Journal ArticlebioRxiv · September 5, 2024
A broad chemical genetics screen in Mycobacterium tuberculosis (Mtb) to identify inhibitors of established or previously untapped targets for therapeutic development yielded compounds (BRD-8000.3 and BRD-9327) that inhibit the essential efflux pump EfpA. T ...
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Journal ArticlebioRxiv · August 19, 2024
Bacterial membranes are complex and dynamic, arising from an array of evolutionary pressures. One enzyme that alters membrane compositions through covalent lipid modification is MprF. We recently identified that Streptococcus agalactiae MprF synthesizes ly ...
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Journal ArticleProc Natl Acad Sci U S A · August 6, 2024
Invasive fungal diseases are a major threat to human health, resulting in more than 1.5 million annual deaths worldwide. The arsenal of antifungal therapeutics remains limited and is in dire need of drugs that target additional biosynthetic pathways that a ...
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Journal ArticleSci Adv · May 31, 2024
Streptococcus agalactiae [group B Streptococcus (GBS)] is a leading cause of neonatal meningitis, with late-onset disease (LOD) occurring after gastrointestinal tract colonization in infants. Bacterial membrane lipids are essential for host-pathogen intera ...
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Journal ArticleJ Biol Chem · May 2024
Sphingolipids are produced by nearly all eukaryotes where they play significant roles in cellular processes such as cell growth, division, programmed cell death, angiogenesis, and inflammation. While it was previously believed that sphingolipids were quite ...
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Journal ArticleSmall · April 2024
A new Yersinia pseudotuberculosis mutant strain, YptbS46, carrying the lpxE insertion and pmrF-J deletion is constructed and shown to exclusively produce monophosphoryl lipid A (MPLA) having adjuvant properties. Outer membrane vesicles (OMVs) isolated from ...
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Journal ArticleMucosal Immunol · April 2024
Streptococcus pneumoniae (Spn) is a common pathogen causing a secondary bacterial infection following influenza, which leads to severe morbidity and mortality during seasonal and pandemic influenza. Therefore, there is an urgent need to develop bacterial v ...
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Journal ArticleBiochemistry · October 17, 2023
Covalent modification of lipid A with 4-deoxy-4-amino-l-arabinose (Ara4N) mediates resistance to cationic antimicrobial peptides and polymyxin antibiotics in Gram-negative bacteria. The proteins required for Ara4N biosynthesis are encoded in the pmrE and a ...
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Journal ArticleSci Transl Med · August 9, 2023
The UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC is an essential enzyme in the biosynthesis of lipid A, the outer membrane anchor of lipopolysaccharide and lipooligosaccharide in Gram-negative bacteria. The development of LpxC-targeting a ...
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Journal ArticleJ Biol Chem · July 2023
A common feature among nearly all gram-negative bacteria is the requirement for lipopolysaccharide (LPS) in the outer leaflet of the outer membrane. LPS provides structural integrity to the bacterial membrane, which aids bacteria in maintaining their shape ...
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Journal ArticlemBio · April 25, 2023
Clostridioides difficile is a Gram-positive opportunistic pathogen responsible for 250,000 hospital-associated infections, 12,000 hospital-associated deaths, and $1 billion in medical costs in the United States each year. There has been recent interest in ...
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Journal ArticleJ Antimicrob Chemother · March 2, 2023
OBJECTIVES: Polymyxins, including colistin, are the drugs of last resort to treat MDR bacterial infections in humans. In-depth understanding of the molecular basis and regulation of polymyxin resistance would provide new therapeutic opportunities to combat ...
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Journal ArticleNat Struct Mol Biol · March 2023
The mycolic acid layer of the Mycobacterium tuberculosis cell wall is essential for viability and virulence, and the enzymes responsible for its synthesis are targets for antimycobacterial drug development. Polyketide synthase 13 (Pks13) is a module encodi ...
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Journal ArticleJ Biol Chem · February 2023
The attachment of a sugar to a hydrophobic lipid carrier is the first step in the biosynthesis of many glycoconjugates. In the halophilic archaeon Haloarcula hispanica, HAH_1206, renamed AepG, is a predicted glycosyltransferase belonging to the CAZy Group ...
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Journal ArticlebioRxiv · January 28, 2023
Mycobacterium tuberculosis is currently the leading cause of death by any bacterial infection1. The mycolic acid layer of the cell wall is essential for viability and virulence, and the enzymes responsible for its synthesis are therefore front line targets ...
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Journal ArticleFEMS Microbiol Lett · January 17, 2023
Although Halobacterim salinarum provided the first example of N-glycosylation outside the Eukarya, only recently has attention focused on delineating the pathway responsible for the assembly of the N-linked tetrasaccharide decorating selected proteins in t ...
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Journal ArticleEMBO Rep · December 6, 2022
Autophagy has emerged as the prime machinery for implementing organelle quality control. In the context of mitophagy, the ubiquitin E3 ligase Parkin tags impaired mitochondria with ubiquitin to activate autophagic degradation. Although ubiquitination is es ...
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Journal ArticleCarbohydr Res · November 2022
Halobacterium salinarum, a halophilic archaeon that grows at near-saturating salt concentrations, provided the first example of N-glycosylation outside Eukarya. Yet, almost 50 years later, numerous aspects of such post-translational protein processing in t ...
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Journal ArticleNat Struct Mol Biol · July 2022
Chitin is an essential component of the fungal cell wall. Chitin synthases (Chss) catalyze chitin formation and translocation across the membrane and are targets of antifungal agents, including nikkomycin Z and polyoxin D. Lack of structural insights into ...
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Journal ArticleCell Rep · May 31, 2022
Lipid A, the membrane-anchored portion of lipopolysaccharide (LPS), is an essential component of the outer membrane (OM) of nearly all Gram-negative bacteria. Here we identify regulatory and structural factors that together render lipid A nonessential in C ...
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Journal ArticleFASEB J · May 2022
Bacteria synthesize numerous types of sphingolipids with various physiological functions. Despite their roles in mediating host inflammation, cellular differentiation, and protection from environmental stress, their biosynthetic pathway remains undefined s ...
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Journal ArticleNature · May 2022
NPR1 is a master regulator of the defence transcriptome induced by the plant immune signal salicylic acid1-4. Despite the important role of NPR1 in plant immunity5-7, understanding of its regulatory mechanisms has been hindered by a l ...
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Journal ArticleProc Natl Acad Sci U S A · March 15, 2022
SignificanceYersinia pestis, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. This plague bacillus has been used as a biological weapon during human history and is currently one of the de ...
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Journal ArticleNat Chem Biol · March 2022
The bacterial domain produces numerous types of sphingolipids with various physiological functions. In the human microbiome, commensal and pathogenic bacteria use these lipids to modulate the host inflammatory system. Despite their growing importance, thei ...
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Journal ArticlePLoS Biol · February 2022
Bacterial membrane lipids are critical for membrane bilayer formation, cell division, protein localization, stress responses, and pathogenesis. Despite their critical roles, membrane lipids have not been fully elucidated for many pathogens. Here, we report ...
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Journal ArticleJ Bacteriol · January 18, 2022
Haloferax volcanii AglD is currently the only archaeal dolichol phosphate (DolP)-mannose synthase shown to participate in N-glycosylation. However, the relation between AglD and Pyrococcus furiosus PF0058, the only archaeal DolP-mannose synthase for which ...
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Journal ArticleProc Natl Acad Sci U S A · January 11, 2022
Hemachromatosis (iron-overload) increases host susceptibility to siderophilic bacterial infections that cause serious complications, but the underlying mechanisms remain elusive. The present study demonstrates that oral infection with hyperyersiniabactin ( ...
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Journal ArticleGlycobiology · December 30, 2021
Although Halobacterium salinarum provided the first example of N-glycosylation outside the Eukarya, much regarding such post-translational modification in this halophilic archaea remains either unclear or unknown. The composition of an N-linked glycan deco ...
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Journal ArticlemSphere · October 27, 2021
Along with surging threats and antibiotic resistance of Pseudomonas aeruginosa in health care settings, it is imperative to develop effective vaccines against P. aeruginosa infection. In this study, we used an Asd (aspartate-semialdehyde dehydrogenase)-bas ...
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Journal ArticleInfect Immun · October 15, 2021
To develop an effective Pseudomonas aeruginosa outer-membrane-vesicle (OMV) vaccine, we eliminated multiple virulence factors from a wild-type (WT) P. aeruginosa strain, PA103, to generate a recombinant strain, PA-m14. Strain PA-m14 was tailored with a pSM ...
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Journal ArticleBiochim Biophys Acta Mol Cell Biol Lipids · September 2021
Studies of the lipidomes of twenty-one species of clostridia have revealed considerable diversity. Even among those species now defined as Clostridium sensu stricto, which are related to Clostridium butyricum, the type species, lipid analysis has shown tha ...
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Journal ArticleEnviron Microbiol · May 2021
Sulfonolipids (SLs) are bacterial lipids that are structurally related to sphingolipids. Synthesis of this group of lipids seems to be mainly restricted to Flavobacterium, Cytophaga and other members of the phylum Bacteroidetes. These lipids have a wide ra ...
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Journal ArticleMicrobiology (Reading) · May 2021
Streptococcus pneumoniae, S. pyogenes (Group A Streptococcus; GAS) and S. agalactiae (Group B Streptococcus; GBS) are major aetiological agents of diseases in humans. The cellular membrane, a crucial site in host-pathogen interactions, is poorly characteri ...
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Journal ArticleMicroorganisms · March 22, 2021
Polymyxins, such as colistin and polymyxin B, are the drugs used as a last resort to treat multidrug-resistant Gram-negative bacterial infections in humans. Increasing colistin resistance has posed a serious threat to human health, warranting in-depth mech ...
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Journal ArticlemSphere · February 24, 2021
Lipoteichoic acid (LTA) is a Gram-positive bacterial cell surface polymer that participates in host-microbe interactions. It was previously reported that the major human pathogen Streptococcus pneumoniae and the closely related oral commensals S. mitis and ...
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Journal ArticleFront Microbiol · 2021
Whereas N-glycosylation is a seemingly universal process in Archaea, pathways of N-glycosylation have only been experimentally verified in a mere handful of species. Toward expanding the number of delineated archaeal N-glycosylation pathways, the involveme ...
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Journal ArticlePLoS Biol · December 2020
Coordination of cell growth is essential for the development of the brain, but the molecular mechanisms underlying the regulation of glial and neuronal size are poorly understood. To investigate the mechanisms involved in glial size regulation, we used Cae ...
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Journal ArticleSci Adv · June 2020
The distribution of phospholipids across the inner membrane (IM) of Gram-negative bacteria is unknown. We demonstrate that the IMs of Escherichia coli and Yersinia pseudotuberculosis are asymmetric, with a 75%/25% (cytoplasmic/periplasmic leaflet) distribu ...
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Journal ArticleMolecules · March 20, 2020
A2E (N-retinylidene-N-retinylethanolamine) is a major fluorophore in the RPE (retinal pigment epithelium). To identify and characterize A2E-rich RPE lipofuscin, we fractionated RPE granules from human donor eyes into five fractions (F1-F5 in ascending orde ...
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Journal ArticleNat Metab · March 2020
Critical to the bacterial stringent response is the rapid relocation of resources from proliferation toward stress survival through the respective accumulation and degradation of (p)ppGpp by RelA and SpoT homologues. While mammalian genomes encode MESH1, a ...
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Journal ArticleSci Rep · February 19, 2020
Lipofuscin in the retinal pigment epithelium (RPE) is the major source of fundus autofluorescence (FAF). A technical challenge to accurately quantify the FAF intensities, thus the lipofuscin concentration, is to compensate the light attenuation of RPE mela ...
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Journal ArticleCell Host Microbe · February 12, 2020
Gram-negative bacteria release outer membrane vesicles into the external milieu to deliver effector molecules that alter the host and facilitate virulence. Vesicle formation is driven by phospholipid accumulation in the outer membrane and regulated by the ...
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Journal ArticleJ Biol Chem · January 31, 2020
Glycan biosynthesis relies on nucleotide sugars (NSs), abundant metabolites that serve as monosaccharide donors for glycosyltransferases. In vivo, signal-dependent fluctuations in NS levels are required to maintain normal cell physiology and are dysregulat ...
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Journal ArticleFront Mol Biosci · 2020
The genus Burkholderia sensu lato is composed of a diverse and metabolically versatile group of bacterial species. One characteristic thought to be unique for the genus Burkholderia is the presence of two forms each (with and without 2-hydroxylation) of th ...
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Journal ArticleBlood Adv · November 26, 2019
We previously reported the discovery of a novel lipid deacetylase in platelets, arylacetamide deacetylase-like 1 (AADACL1/NCEH1), and that its inhibition impairs agonist-induced platelet aggregation, Rap1 GTP loading, protein kinase C (PKC) activation, and ...
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Journal ArticleJ Bacteriol · November 15, 2019
The mitis group streptococci include the major human pathogen Streptococcus pneumoniae and the opportunistic pathogens Streptococcus mitis and Streptococcus oralis, which are human oral cavity colonizers and agents of bacteremia and infective endocarditis ...
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Journal ArticleArch Biochem Biophys · October 30, 2019
Long-chain polyprenol phosphates feature in membrane-associated glycoconjugate biosynthesis pathways across domains of life. These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phos ...
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Journal ArticleLipids · August 2019
The lipidomes of Clostridium fallax and Clostridium cadaveris were studied using thin-layer chromatography (TLC) and normal phase liquid chromatography/mass spectrometry (NPLC/MS). Both species contain diradylglycerol (DRG), monohexosyldiradylglycerol (MHD ...
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Journal ArticlemBio · June 18, 2019
Although distinct lipid phosphatases are thought to be required for processing lipid A (component of the outer leaflet of the outer membrane), glycerophospholipid (component of the inner membrane and the inner leaflet of the outer membrane), and undecapren ...
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Journal ArticleNat Commun · April 15, 2019
The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases. MurJ is the flippase for the lipi ...
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Journal ArticlemBio · April 2, 2019
Caulobacter crescentus adapts to phosphate starvation by elongating its cell body and a polar stalk structure. The stalk is an extension of the Gram-negative envelope containing inner and outer membranes as well as a peptidoglycan cell wall. Cellular elong ...
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Journal ArticleMol Microbiol · August 2018
The mechanisms by which micro-organisms sense and internalize extracellular pH signals are not completely understood. One example of a known external pH-sensing process is the fungal-specific Rim/Pal signal transduction pathway. Fungi, such as the opportun ...
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Journal ArticleOphthalmology · May 2018
PURPOSE: To analyze the genetic and clinical findings in retinitis pigmentosa (RP) patients of Ashkenazi Jewish (AJ) descent, aiming to identify genotype-phenotype correlations. DESIGN: Cohort study. PARTICIPANTS: Retinitis pigmentosa patients from 230 fam ...
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Journal ArticleJ Biol Chem · March 2, 2018
Secretory phospholipases A2 (sPLA2s) are potent components of mammalian innate-immunity antibacterial mechanisms. sPLA2 enzymes attack bacteria by hydrolyzing bacterial membrane phospholipids, causing membrane disorganization and cell lysis. However, most ...
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Journal ArticleAntimicrob Agents Chemother · January 2018
Vancomycin-resistant Enterococcus faecium strains (VREfm) are critical public health concerns because they are among the leading causes of hospital-acquired bloodstream infections. Chlorhexidine (CHX) is a bisbiguanide cationic antiseptic that is routinely ...
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Journal ArticleFEMS Microbiol Lett · January 1, 2018
The cell membrane of (hyper)thermophilic archaea, including the thermoacidophile Sulfolobus acidocaldarius, incorporates dibiphytanylglycerol tetraether lipids. The hydrophobic cores of such tetraether lipids can include up to eight cyclopentane rings. Pre ...
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Journal ArticleGenetics · December 2017
Dolichols are isoprenoid lipids of varying length that act as sugar carriers in glycosylation reactions in the endoplasmic reticulum. In Saccharomyces cerevisiae, there are two cis-prenyltransferases that synthesize polyprenol-an essential precursor to dol ...
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Journal ArticleEMBO J · November 2, 2017
Methionine metabolism is critical for epigenetic maintenance, redox homeostasis, and animal development. However, the regulation of methionine metabolism remains unclear. Here, we provide evidence that SIRT1, the most conserved mammalian NAD+-dependent pro ...
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Journal ArticleBiochimie · October 2017
Bacteria belonging to the genus Streptomyces are among the most prolific producers of antibiotics. Research on cellular membrane biosynthesis and turnover is lagging behind in Streptomyces compared to related organisms like Mycobacterium tuberculosis. Whil ...
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Journal ArticleBioconjug Chem · September 20, 2017
N-glycosylation, the covalent attachment of glycans to select protein target Asn residues, is a post-translational modification performed by all three domains of life. In the halophilic archaea Haloferax volcanii, in which understanding of this universal p ...
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Journal ArticleBiochim Biophys Acta Mol Cell Biol Lipids · June 2017
N-glycosylation, a post-translational modification whereby glycans are covalently linked to select Asn residues of target proteins, occurs in all three domains of life. Across evolution, the N-linked glycans are initially assembled on phosphorylated cytopl ...
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Journal ArticleAntimicrob Agents Chemother · May 2017
Synthesis and integrity of the cytoplasmic membrane are fundamental to cellular life. Experimental evolution studies have hinted at unique physiology in the Gram-positive bacteria Streptococcus mitis and S. oralis These organisms commonly cause bacteremia ...
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Journal ArticleMol Microbiol · March 2017
Treponema denticola synthesizes phosphatidylcholine through a licCA-dependent CDP-choline pathway identified only in the genus Treponema. However, the mechanism of conversion of CDP-choline to phosphatidylcholine remained unclear. We report here characteri ...
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Journal ArticleJ Biol Chem · November 25, 2016
Phosphatidylglycerol (PG) makes up 5-20% of the phospholipids of Escherichia coli and is essential for growth in wild-type cells. PG is synthesized from the dephosphorylation of its immediate precursor, phosphatidylglycerol phosphate (PGP) whose synthase i ...
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Journal ArticleBiochim Biophys Acta · September 2016
We have examined the lipids of three isolates, Romboutsia lituseburensis, Romboutsia ilealis, and Romboutsia sp. strain FRIFI, of the newly described genus Romboutsia by two-dimensional thin-layer chromatography (2D-TLC) and by liquid chromatography/mass s ...
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Journal ArticleFEBS Lett · September 2016
N-glycosylation is a post-translational modification that occurs across evolution. In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eu ...
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Journal ArticlemBio · March 22, 2016
Constitutive biosynthesis of lipid A via the Raetz pathway is essential for the viability and fitness of Gram-negative bacteria, includingChlamydia trachomatis Although nearly all of the enzymes in the lipid A biosynthetic pathway are highly conserved acro ...
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Journal ArticleEMBO Rep · February 2016
NgBR is a transmembrane protein identified as a Nogo-B-interacting protein and recently has been shown to be a subunit required for cis-prenyltransferase (cisPTase) activity. To investigate the integrated role of NgBR in vascular development, we have chara ...
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Journal ArticleJ Biol Chem · January 29, 2016
Lysophospholipid transporter (LplT) was previously found to be primarily involved in 2-acyl lysophosphatidylethanolamine (lyso-PE) recycling in Gram-negative bacteria. This work identifies the potent role of LplT in maintaining membrane stability and integ ...
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Journal ArticleNat Commun · January 5, 2016
The attachment of a sugar to a hydrophobic polyisoprenyl carrier is the first step for all extracellular glycosylation processes. The enzymes that perform these reactions, polyisoprenyl-glycosyltransferases (PI-GTs) include dolichol phosphate mannose synth ...
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Journal ArticleJ Am Chem Soc · October 7, 2015
The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. Studies to advance our understanding of these interactions rely on th ...
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Journal ArticleEnviron Microbiol · May 2015
Ornithine lipids (OLs) are phosphorus-free membrane lipids that can be formed by many bacteria but that are absent from archaea and eukaryotes. A function for OLs in stress conditions and in host-bacteria interactions has been shown in some bacteria. Some ...
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Journal ArticleJ Lipid Res · March 2015
The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility an ...
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Journal ArticlePLoS One · 2015
In all three domains of life, N-glycosylation begins with the assembly of glycans on phosphorylated polyisoprenoid carriers. Like eukaryotes, archaea also utilize phosphorylated dolichol for this role, yet whereas the assembled oligosaccharide is transferr ...
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Journal ArticleBiochim Biophys Acta · October 2014
Analysis of the polar lipids of many pathogenic and non-pathogenic clostridia has revealed the presence of plasmalogens, alk-1'-enyl ether-containing phospholipids and glycolipids. An exception to this finding so far has been Clostridium difficile, an impo ...
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Journal ArticleBiochem Biophys Res Commun · September 26, 2014
The lipopolysaccharide (LPS) isolated from certain important Gram-negative pathogens including a human pathogen Yersinia pestis and opportunistic pathogens Burkholderia mallei and Burkholderia pseudomallei contains d-glycero-d-talo-oct-2-ulosonic acid (Ko) ...
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Journal ArticleCell Metab · September 2, 2014
Dolichol is an obligate carrier of glycans for N-linked protein glycosylation, O-mannosylation, and GPI anchor biosynthesis. cis-prenyltransferase (cis-PTase) is the first enzyme committed to the synthesis of dolichol. However, the proteins responsible for ...
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Journal ArticleJ Bacteriol · April 2014
Bacterial lipases play important roles in bacterial metabolism and environmental response. Our laboratory recently discovered that a novel lipoprotein lysophospholipase, VolA, localizes on the surface of the Gram-negative aquatic pathogen Vibrio cholerae. ...
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Journal ArticleAppl Environ Microbiol · January 2014
Across evolution, N-glycosylation involves oligosaccharyltransferases that transfer lipid-linked glycans to selected Asn residues of target proteins. While these enzymes catalyze similar reactions in each domain, differences exist in terms of the chemical ...
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Journal ArticleJ Lipid Res · December 2013
We observed a characteristic shortening of plasma and urinary dolichols in retinitis pigmentosa (RP) patients carrying K42E and T206A mutations in the dehydrodolichol diphosphate synthase (DHDDS) gene, using liquid chromatography-mass spectrometry. Dolicho ...
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Journal ArticlemBio · November 5, 2013
UNLABELLED: N-glycosylation in Archaea presents aspects of this posttranslational modification not seen in either Eukarya or Bacteria. In the haloarchaeon Haloferax volcanii, the surface (S)-layer glycoprotein can be simultaneously modified by two differen ...
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Journal ArticleScience · August 30, 2013
MraY (phospho-MurNAc-pentapeptide translocase) is an integral membrane enzyme that catalyzes an essential step of bacterial cell wall biosynthesis: the transfer of the peptidoglycan precursor phospho-MurNAc-pentapeptide to the lipid carrier undecaprenyl ph ...
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Journal ArticlemBio · July 23, 2013
UNLABELLED: Treatment of multidrug-resistant enterococci has become a challenging clinical problem in hospitals around the world due to the lack of reliable therapeutic options. Daptomycin (DAP), a cell membrane-targeting cationic antimicrobial lipopeptide ...
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Journal ArticleBiochim Biophys Acta · June 2013
We have examined the polar lipids of Clostridium psychrophilum, a recently characterized psychrophilic Clostridium isolated from an Antarctic microbial mat. Lipids were extracted from cells grown near the optimal growth temperature (+5°C) and at -5°C, and ...
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Journal ArticleBiochim Biophys Acta · June 2013
Two phosphorus-containing glycolipids have previously been observed in Clostridium acetobutylicum. We had shown that the concentration of one of them increases in response to increased unsaturation of the membrane lipid hydrocarbon chains, suggesting a pot ...
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Journal ArticlemBio · May 14, 2013
UNLABELLED: Previous work from our laboratory showed that the Gram-negative aquatic pathogen Vibrio cholerae can take up a much wider repertoire of fatty acids than other Gram-negative organisms. The current work elaborated on the ability of V. cholerae to ...
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Journal ArticleEnviron Microbiol · March 2013
Ornithine lipids (OLs) are phosphorus-free membrane lipids that are widespread among Gram-negative bacteria. Their basic structure consists of a 3-hydroxy fatty acyl group attached in amide linkage to the α-amino group of ornithine and a second fatty acyl ...
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Journal ArticleBiochim Biophys Acta · March 2013
The S-layer glycoprotein is the sole component of the protein shell surrounding Haloferax volcanii cells. The deduced amino acid sequence of the S-layer glycoprotein predicts the presence of a C-terminal membrane-spanning domain. However, several earlier o ...
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Journal ArticleJ Biol Chem · February 22, 2013
LpxC, the deacetylase that catalyzes the second and committed step of lipid A biosynthesis in Escherichia coli, is an essential enzyme in virtually all gram-negative bacteria and is one of the most promising antibiotic targets for treatment of multidrug-re ...
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Journal ArticlePLoS One · 2013
N-glycosylation is a post-translational modification performed by members of all three domains of life. Studies on the halophile Haloferax volcanii have offered insight into the archaeal version of this universal protein-processing event. In the present st ...
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Journal ArticleEur J Immunol · January 2013
Mast cells play a critical role in the pathogenesis of allergic diseases; however, how mast cell function is regulated is still not well understood. Both phosphatidic acid (PA) and diacylglycerol (DAG) are important secondary messengers involved in mast ce ...
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Journal ArticleScience · 2013
MraY (phospho-MurNAc-pentapeptide translocase) is an integral membrane enzyme that catalyzes an essential step of bacterial cell wall biosynthesis: the transfer of the peptidoglycan precursor phospho-MurNAc-pentapeptide to the lipid carrier undecaprenyl ph ...
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Journal ArticleProc Natl Acad Sci U S A · October 9, 2012
Depending on growth phase and culture conditions, cardiolipin (CL) makes up 5-15% of the phospholipids in Escherichia coli with the remainder being primarily phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). In E. coli, the cls and ybhO genes (r ...
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Journal ArticleMicrobiology (Reading) · October 2012
Clostridium botulinum has been classified into four groupings (groups I to IV) based on physiological characteristics and 16S rRNA sequencing. We have examined the lipid compositions of 11 representative strains of C. botulinum and a strain of Clostridium ...
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Journal ArticleBiochim Biophys Acta · October 2012
BACKGROUND: Recent studies of Haloferax volcanii have begun to elucidate the steps of N-glycosylation in Archaea, where this universal post-translational modification remains poorly described. In Hfx. volcanii, a series of Agl proteins catalyzes the assemb ...
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Journal ArticleCell Rep · September 27, 2012
HipA is a bacterial serine/threonine protein kinase that phosphorylates targets, bringing about persistence and multidrug tolerance. Autophosphorylation of residue Ser150 is a critical regulatory mechanism of HipA function. Intriguingly, Ser150 is not loca ...
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Journal ArticleJ Biol Chem · July 20, 2012
Type II topoisomerases are essential enzymes for solving DNA topological problems by passing one segment of DNA duplex through a transient double-strand break in a second segment. The reaction requires the enzyme to precisely control DNA cleavage and gate ...
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Journal ArticleBiochim Biophys Acta · June 2012
In N-glycosylation in both Eukarya and Archaea, N-linked oligosaccharides are assembled on dolichol phosphate prior to transfer of the glycan to the protein target. However, whereas only the α-position isoprene subunit is saturated in eukaryal dolichol pho ...
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Journal ArticleMol Microbiol · May 2012
VP4, the major structural protein of the haloarchaeal pleomorphic virus, HRPV-1, is glycosylated. To define the glycan structure attached to this protein, oligosaccharides released by β-elimination were analysed by mass spectrometry and nuclear magnetic re ...
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Journal ArticleMol Genet Metab · April 2012
Congenital disorders of glycosylation (CDG) are caused by a dysfunction of glycosylation, an essential step in the manufacturing process of glycoproteins. This paper focuses on a 6-year-old patient with a new type of CDG-I caused by a defect of the steroid ...
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Journal ArticleEnviron Microbiol · March 2012
To cope with life in hypersaline environments, halophilic archaeal proteins are enriched in acidic amino acids. This strategy does not, however, offer a response to transient changes in salinity, as would post-translational modifications. To test this hypo ...
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Journal ArticlePLoS One · 2012
BACKGROUND: The lipopeptide antibiotic, daptomycin (DAP) interacts with the bacterial cell membrane (CM). Development of DAP resistance during therapy in a clinical strain of Enterococcus faecalis was associated with mutations in genes encoding enzymes inv ...
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Journal ArticleBiochim Biophys Acta · November 2011
Across evolution, dolichols and polyprenols serve as sugar carriers in biosynthetic processes that include protein glycosylation and lipopolysaccharide biogenesis. Liquid chromatography coupled with electrospray ionization mass spectrometry offers a powerf ...
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Journal ArticleBiochim Biophys Acta · November 2011
Electrospray ionization mass spectrometry is a powerful technique to analyze lipid extracts especially for the identification of new lipid metabolites. A hurdle to lipid identification is the presence of solvent contaminants that hinder the identification ...
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Journal ArticleJ Biol Chem · October 28, 2011
The CD1 family consists of five proteins that are related to the peptide-presenting MHC class I family. T cells can recognize the presentation of both foreign and self-derived lipids on four CD1 family members. The identities of the self-lipids capable of ...
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Journal ArticleBiochim Biophys Acta · October 2011
Polyprenoids, polymers containing varied numbers of isoprene subunits, serve numerous roles in biology. In Eukarya, dolichyl phosphate, a phosphorylated polyprenol bearing a saturated α-end isoprene subunit, serves as the glycan carrier during N-glycosylat ...
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Journal ArticleJ Biol Chem · September 23, 2011
Studies in animal models have indicated that dietary isothiocyanates (ITCs) exhibit cancer preventive activities through carcinogen detoxification-dependent and -independent mechanisms. The carcinogen detoxification-independent mechanism of cancer preventi ...
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Journal ArticleMol Microbiol · September 2011
Recent insight into the N-glycosylation pathway of the haloarchaeon, Haloferax volcanii, is helping to bridge the gap between our limited understanding of the archaeal version of this universal post-translational modification and the better-described eukar ...
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Journal ArticleProc Natl Acad Sci U S A · July 12, 2011
The lipid A moiety of Escherichia coli lipopolysaccharide is a hexa-acylated disaccharide of glucosamine that makes up the outer monolayer of the outer membrane. Arabidopsis thaliana contains nuclear genes encoding orthologs of key enzymes of bacterial lip ...
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Journal ArticleMicrob Biotechnol · July 2011
Archaeal glycoproteins present a variety of N-linked glycans not seen elsewhere. The ability to harness the agents responsible for this unparalleled diversity offers the possibility of generating glycoproteins bearing tailored glycans, optimized for specif ...
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Journal ArticleCell Metab · June 8, 2011
PTPMT1 was the first protein tyrosine phosphatase found localized to the mitochondria, but its biological function was unknown. Herein, we demonstrate that whole body deletion of Ptpmt1 in mice leads to embryonic lethality, suggesting an indispensable role ...
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Journal ArticleJ Nat Prod · March 25, 2011
Platensimycin (1a) and platencin (2) are inhibitors of FabF and FabF/H bacterial fatty acid synthase. The discovery of natural congeners is an approach that can render a better understanding of the structure-function relationships of complex natural produc ...
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Journal ArticleMol Microbiol · March 2011
Ornithine lipids (OLs) are widespread among Gram-negative bacteria. Their basic structure consists of a 3-hydroxy fatty acyl group attached in amide linkage to the α-amino group of ornithine and a second fatty acyl group ester-linked to the 3-hydroxy posit ...
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Journal ArticleBiochim Biophys Acta · March 2011
A study of the polar lipids of Clostridium novyi NT has revealed the presence of phosphatidylethanolamine (PE) and cardiolipin as major phospholipids with smaller amounts of phosphatidylglycerol (PG), lysyl-PG and alanyl-PG. Other minor phospholipids inclu ...
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Journal ArticleJ Biol Chem · February 18, 2011
The phospholipids of Escherichia coli consist mainly of phosphatidylethanolamine, phosphatidylglycerol (PG), and cardiolipin. PG makes up ∼25% of the cellular phospholipid and is essential for growth in wild-type cells. PG is synthesized on the inner surfa ...
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Journal ArticleAnal Biochem · February 15, 2011
Two homologous 29 amino acid-long highly hydrophobic membrane miniproteins were identified in the Bligh-Dyer lipid extracts of Escherichia coli and Salmonella typhimurium using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The amino acid seque ...
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Journal ArticleMol Microbiol · February 2011
The Gram-negative bacteria Vibrio cholerae poses significant public health concerns by causing an acute intestinal infection afflicting millions of people each year. V. cholerae motility, as well as virulence factor expression and outer membrane protein pr ...
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Journal ArticleJ Biol Chem · December 17, 2010
We report the lipidomic response of the murine macrophage RAW cell line to Kdo(2)-lipid A, the active component of an inflammatory lipopolysaccharide functioning as a selective TLR4 agonist and compactin, a statin inhibitor of cholesterol biosynthesis. Ana ...
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Journal ArticleMol Microbiol · December 2010
In Archaea, dolichol phosphates have been implicated as glycan carriers in the N-glycosylation pathway, much like their eukaryal counterparts. To clarify this relation, highly sensitive liquid chromatography/mass spectrometry was employed to detect and cha ...
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Journal ArticleGlycobiology · December 2010
During evolution the average chain length of polyisoprenoid glycosyl carrier lipids increased from C55 (prokaryotes) to C75 (yeast) to C95 (mammalian cells). In this study, the ability of the E. coli enzyme, undecaprenyl pyrophosphate synthase (UPPS), to c ...
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Journal ArticleJ Lipid Res · November 2010
The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids. Partial lipid analysis is now a regular part of every patient's blood test and physician ...
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Journal ArticleJ Bacteriol · November 2010
Like the Eukarya and Bacteria, the Archaea also perform N glycosylation. Using the haloarchaeon Haloferax volcanii as a model system, a series of Agl proteins involved in the archaeal version of this posttranslational modification has been identified. In t ...
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Journal ArticleInt J Exp Pathol · October 2010
Granuloma formation is an inflammatory response of the host against invading pathogens or indigestible substances. We generated mesenteric oil granulomas by injecting pristane into the peritoneal cavity (PC) of mice, and compared oil granuloma formation in ...
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Journal ArticleJ Lipid Res · September 2010
Lipids orchestrate biological processes by acting remotely as signaling molecules or locally as membrane components that modulate protein function. Detailed insight into lipid function requires knowledge of the subcellular localization of individual lipids ...
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Journal ArticleProc Natl Acad Sci U S A · August 24, 2010
Phosphatidylcholine (PC) has been widely used in place of naturally occurring phosphatidylethanolamine (PE) in reconstitution of bacterial membrane proteins. However, PC does not support native structure or function for several reconstituted transport prot ...
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Journal ArticleCell · July 23, 2010
N-linked glycosylation is the most frequent modification of secreted and membrane-bound proteins in eukaryotic cells, disruption of which is the basis of the congenital disorders of glycosylation (CDGs). We describe a new type of CDG caused by mutations in ...
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Journal ArticleGlycobiology · July 2010
Giardia lamblia, the protist that causes diarrhea, makes an Asn-linked-glycan (N-glycan) precursor that contains just two sugars (GlcNAc(2)) attached by a pyrophosphate linkage to a polyprenol lipid. Because the candidate cis-prenyltransferase of Giardia a ...
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Journal ArticleJ Lipid Res · July 2010
The polar lipids of the anaerobic bacterium Clostridium tetani, the causative agent of tetanus, have been examined by two-dimensional thin layer chromatography, ESI mass spectrometry, and NMR spectroscopy. Plasmalogen and di- and tetra-acylated species of ...
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Journal ArticleInternational Journal of Mass Spectrometry · April 27, 2010
Francisella tularensis is a highly infectious human pathogen that can cause tularemia, but little is known about the lipid composition in membranes of this bacterium. Our recent study has shown that lipid A in membranes of F. tularensis subsp. novicida is ...
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Journal ArticleMol Cell Proteomics · February 2010
Compartmentalization of biological processes and the associated cellular components is crucial for cell function. Typically, the location of a component is revealed through a co-localization and/or co-purification with an organelle marker. Therefore, the i ...
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Journal ArticleProc Natl Acad Sci U S A · January 5, 2010
Rhizobia are Gram-negative soil bacteria able to establish nitrogen-fixing root nodules with their respective legume host plants. Besides phosphatidylglycerol, cardiolipin, and phosphatidylethanolamine, rhizobial membranes contain phosphatidylcholine (PC) ...
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Journal ArticleJ Antibiot (Tokyo) · December 2009
Platensimycin and platencin are inhibitors of FabF and FabF/H bacterial fatty acid synthesis enzymes, respectively. Discovery of natural congeners provides one of the ways to understand the relationship of chemical structure and biological function. Effort ...
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Journal ArticleBiochim Biophys Acta · October 2009
Cells control their own hydration by accumulating solutes when they are exposed to high osmolality media and releasing solutes in response to osmotic down-shocks. Osmosensory transporters mediate solute accumulation and mechanosensitive channels mediate so ...
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Journal ArticleJ Chromatogr B Analyt Technol Biomed Life Sci · September 15, 2009
Discovery and structural elucidation of novel brain lipids hold great promise in revealing new lipid functions in the brain and in understanding the biochemical mechanisms underlying brain physiology and pathology. The revived interests in searching for no ...
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Journal ArticleJ Biol Chem · June 26, 2009
Cardiolipin (CL) is an anionic membrane lipid present in bacteria, plants, and animals, but absent from archaea. It is generally thought that bacteria use an enzyme belonging to the phospholipase D superfamily as cardiolipin synthase (Cls) catalyzing a rev ...
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Journal ArticleBiochemistry · April 14, 2009
The UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC catalyzes the committed reaction of lipid A (endotoxin) biosynthesis in Gram-negative bacteria and is a validated antibiotic target. Although several previously described compounds bind to ...
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Journal ArticleJ Lipid Res · April 2009
The outer monolayer of the outer membrane of Gram-negative bacteria consists of the lipid A component of lipopolysaccharide (LPS), a glucosamine-based saccharolipid that is assembled on the inner surface of the inner membrane. The first six enzymes of the ...
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Journal ArticleBiochemistry · February 17, 2009
Francisella tularensis is a highly infectious pathogen that causes tularemia. Francisella lipid A contains an unusual galactosamine (GalN) unit, attached to its 1-phosphate moiety. Two genes, flmF2 and flmK, are required for the addition of GalN to Francis ...
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Journal ArticleBiochemistry · February 17, 2009
Lipid A of Francisella tularensis subsp. novicida contains a galactosamine (GalN) residue linked to its 1-phosphate group. As shown in the preceding paper, this GalN unit is transferred to lipid A from the precursor undecaprenyl phosphate-beta-D-GalN. A sm ...
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Journal ArticleBiochemistry · August 19, 2008
Escherichia coli lipid A is a hexaacylated disaccharide of glucosamine with secondary laurate and myristate chains on the distal unit. Hexaacylated lipid A is a potent agonist of human Toll-like receptor 4, whereas its tetra- and pentaacylated precursors a ...
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Journal ArticleEukaryot Cell · August 2008
Trichomonas vaginalis, the protist that causes vaginal itching, has a huge genome with numerous gene duplications. Recently we found that Trichomonas has numerous genes encoding putative dolichyl-phosphate-glucose (Dol-P-Glc) synthases (encoded by ALG5 gen ...
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Journal ArticleAnal Chem · August 1, 2008
Phosphorylation plays vital roles in the regulation and function of the V2 vasopressin receptor (V2R), a G protein-coupled receptor (GPCR) that is responsible for maintaining water homeostasis in the kidney. Through a combination of immunoaffinity purifica ...
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Journal ArticleBiochemistry · March 4, 2008
The lipid A residues of certain Gram-negative bacteria, including most strains of Salmonella and Pseudomonas, are esterified with one or two secondary S-2-hydroxyacyl chains. The S-2 hydroxylation process is O 2-dependent in vivo, but the relevant enzymati ...
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Journal ArticleBiochemistry · December 18, 2007
While profiling the lipidome of the mouse brain by mass spectrometry, we discovered a novel family of N-acylphosphatidylserine (N-acyl-PS) molecules. These N-acyl-PS species were enriched by DEAE-cellulose column chromatography, and they were then characte ...
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Journal ArticleJ Biol Chem · December 7, 2007
Modification of lipid A with the 4-amino-4-deoxy-L-arabinose (L-Ara4N) moiety is required for resistance to polymyxin and cationic antimicrobial peptides in Escherichia coli and Salmonella typhimurium. An operon of seven genes (designated pmrHFIJKLM in S. ...
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Journal ArticleMol Plant Microbe Interact · November 2007
Lysyl-phosphatidylglycerol (LPG) is a well-known membrane lipid in several gram-positive bacteria but is almost unheard of in gram-negative bacteria. In Staphylococcus aureus, the gene product of mprF is responsible for LPG formation. Low pH-inducible gene ...
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Journal ArticleJ Nat Prod · August 2007
Coccidiosis is one of the more common and costly diseases in poultry that is caused by various Eimeria species. In our quest to discover coccidiostats from natural products, we discovered a microbial fermentation extract that exhibited in vivo anticoccidia ...
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Journal ArticleJ Biol Chem · July 20, 2007
beta-Arrestins are multifunctional adaptor proteins that regulate seven transmembrane-spanning receptor (7TMR) desensitization and internalization and also initiate alternative signaling pathways. Studies have shown that beta-arrestins undergo a conformati ...
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Journal ArticleJ Lipid Res · July 2007
Neuromelanin (NM) isolated from the substantia nigra of the human brain is found to contain a series of dolichoic acids (dol-CA) containing 14-20 isoprene units. This is the first observation of dol-CA in a natural system. Using internally spiked nor-dolic ...
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Journal ArticleProc Natl Acad Sci U S A · March 6, 2007
Francisella tularensis causes tularemia, a highly contagious disease of animals and humans, but the virulence features of F. tularensis are poorly defined. F. tularensis and the related mouse pathogen Francisella novicida synthesize unusual lipid A molecul ...
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Journal ArticleMethods Enzymol · 2007
Prenols, a class of lipids formed by the condensation of five carbon isoprenoids, have important roles in numerous metabolic pathways of the eukaryotic cell. Prenols are found in the cell as free alcohols, such as dolichol, or can be attached to vitamins, ...
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Journal ArticleFree Radic Biol Med · December 15, 2006
Human Cu,Zn-superoxide dismutase (hSOD1) has 4 cysteines per subunit. Cys57 and Cys148 are involved in an intrasubunit disulfide bond, while Cys6 and Cys111 are free. Cys6 is buried within the protein while Cys111 is on the surface, near the dimer interfac ...
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Journal ArticleBiochemistry · December 5, 2006
Francisella tularensis subsp. novicida U112 phospholipids, extracted without hydrolysis, consist mainly of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, and two lipid A species, designated A1 and A2. These lipid A species, present in ...
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Journal ArticleBiotechnol Lett · July 2006
Electron capture dissociation (ECD) represents one of the most recent and significant advancements in tandem mass spectrometry (MS/MS) for the identification and characterization of polypeptides. In comparison with the conventional fragmentation techniques ...
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Journal ArticleJ Biol Chem · May 5, 2006
The lipid A and core regions of the lipopolysaccharide in Rhizobium leguminosarum, a nitrogen-fixing plant endosymbiont, are strikingly different from those of Escherichia coli. In R. leguminosarum lipopolysaccharide, the inner core is modified with three ...
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Journal ArticleJ Antibiot (Tokyo) · May 2006
Xanthonol, a novel dimeric xanthone, was isolated from a fermentation broth of a non-sporulating fungal species using Sephadex LH20 followed by HPLC and the structure elucidated by spectral analysis. Xanthonol exhibited insecticidal and anthelmintic activi ...
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Journal ArticleJ Nat Prod · April 2006
Parasite cGMP-dependent protein kinase (PKG) is one of the validated biochemical targets for the treatment of coccidiosis. We screened our library of natural product extracts for inhibitors of parasite PKG for the discovery of anticoccidial leads. Terferol ...
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Journal ArticleBiol Chem · March 2006
ADAM proteases are type I transmembrane proteins with extracellular metalloprotease domains. As for most ADAM family members, ADAM8 (CD156a, MS2) is involved in ectodomain shedding of membrane proteins and is linked to inflammation and neurodegeneration. T ...
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Journal ArticleBiochemistry · December 20, 2005
The zinc-dependent enzyme LpxC catalyzes the deacetylation of UDP-3-O-acyl-GlcNAc, the first committed step of lipid A biosynthesis. Lipid A is an essential component of the outer membranes of most Gram-negative bacteria, including Escherichia coli, Salmon ...
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Journal ArticleProc Natl Acad Sci U S A · December 6, 2005
The phosphorylation state of the C-terminal repeat domain (CTD) of the largest subunit of RNA polymerase II changes as polymerase transcribes a gene, and the distinct forms of the phospho-CTD (PCTD) recruit different nuclear factors to elongating polymeras ...
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Journal ArticleNat Prod Res · December 2005
Geranylgeranyltransferase I (GGTase I) catalyzes the post-translational transfer of lyophilic diterpenoid geranylgeranyl to the cysteine residue of proteins terminating with a CaaX motif such as Rho1p and Cdc42p. It has been shown that GGTase I activity is ...
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Journal ArticleTetrahedron Letters · November 14, 2005
A new method for the synthesis of eight-membered heterocyclic 1,4,5-oxadiazocines has been described from β-diketone and β,β,β-triketone with an acidic α-hydrogen. The method entails the reaction of a di- or triketone with 2-hydroxyethylhydrazine and an al ...
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Journal ArticleJ Antibiot (Tokyo) · November 2005
The chemokine receptor, CCR2, is predominantly expressed on monocytes/macrophages, and on a subset of memory T cells. It binds to several CC type chemokines of the monocyte chemoattractant protein (MCP) family of which MCP-1 exhibits the highest affinity. ...
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Journal ArticleAnal Biochem · October 15, 2005
Undecaprenyl diphosphate-MurNAc-pentapeptide-GlcNAc (lipid II) is extracted from Escherichia coli cells by utilizing its unusual pH-dependent solubility property in a Bligh-Dyer system, and identified by electrospray ionization mass spectrometry in conjunc ...
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Journal ArticleJ Nat Prod · September 2005
Liver X receptors (LXR) are nuclear hormone receptors that play a critical role in cholesterol homeostasis. They regulate the expression of the ABCA1 gene, which mediates the efflux of cholesterol out of cells. LXR agonists are expected to increase cholest ...
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Journal ArticleJ Antibiot (Tokyo) · September 2005
Cholesterol homeostasis is tightly controlled process that involves a variety of regulators including liver X receptors (LXR). Agonists of LXR are expected to increase cholesterol efflux, lower LDL, and raise HDL levels. Screening of a natural product libr ...
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Journal ArticleBiochem Biophys Res Commun · August 19, 2005
Electron capture dissociation (ECD) represents a significant advance in tandem mass spectrometry for the identification and characterization of post-translational modifications (PTMs) of polypeptides. In comparison with the conventional fragmentation techn ...
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Journal ArticleJ Nat Prod · August 2005
It has been demonstrated that liver X receptors (LXR) play a significant role in cholesterol homeostasis. Agonists of LXR are expected to increase cellular cholesterol efflux, lower LDL, and raise HDL levels. Screening of a natural product library of plant ...
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Journal ArticleJ Nat Prod · April 2005
Liver X receptors (LXR) have been implicated in cholesterol homeostasis. Agonists of LXR are expected to increase cholesterol efflux, lower LDL, and raise HDL levels. Screening of a natural product library of plant extracts using a LXR-SPA binding assay an ...
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Journal ArticleJ Nat Prod · April 2005
Parasite cGMP-dependent protein kinase (PKG) has been recently validated as a biochemical target for the treatment of coccidiosis. To discover new anticoccidial leads, we have screened our library of natural product extracts for inhibitors of parasite PKG. ...
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Journal ArticleNat Struct Mol Biol · April 2005
The human nuclear receptor liver receptor homolog 1 (hLRH-1) plays an important role in the development of breast carcinomas. This orphan receptor is efficiently downregulated by the unusual co-repressor SHP and has been thought to be ligand-independent. W ...
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Journal ArticleBiochemistry · February 1, 2005
The first committed step of lipid A biosynthesis in Gram-negative bacteria is catalyzed by the zinc-dependent hydrolase LpxC that removes an acetate from the nitrogen at the 2' '-position of UDP-3-O-acyl-N-acetylglucosamine. Recent structural characterizat ...
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Journal ArticleMol Divers · 2005
The chemokines (CXCL9, CXCL10 and CXCL11) and associated CXCR3 receptor are expressed during the inflammatory process from multiple sclerosis, atherosclerosis or organ transplantation resulting in the recruitment of lymphocytes leading to tissue damage. It ...
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Journal ArticleJ Nat Prod · June 2004
Human CCR5 is a G-coupled receptor that binds to the envelope protein gp120 and CD4 and mediates the HIV-1 viral entry into the cells. The blockade of this binding by a small molecule receptor antagonist could lead to a new mode of action agent for HIV-1 a ...
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ConferenceSPE International Formation Damage Control Symposium Proceedings · May 12, 2004
Sebei Gas Field is in the northeast of Caidam Basin, Qinghai, China. Its main pay-zone is unconsolidation quaternary fine-silty and dirty sandstones with serious sand production. A series of technique of comprehensive sand control with fiber-resin coated s ...
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Journal ArticleJ Nat Prod · May 2004
HIV-1 integrase is a critical enzyme for replication of HIV, and its inhibition is one of the most promising new drug targets for anti-retroviral therapy with potentially significant advantages over existing therapies. In this Note, the isolation, structur ...
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Journal ArticleJ Ind Microbiol Biotechnol · December 2003
HIV-1 integrase is a critical enzyme for replication of HIV, and its inhibition is one of the most promising new drug strategies for anti-retroviral therapy, with potentially significant advantages over existing therapies. In this report, a series of HIV-1 ...
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Journal ArticleHelvetica Chimica Acta · November 20, 2003
HIV-1 Integrase is a critical enzyme for replication of HIV, and its inhibition is one of the most promising new drug targets for anti-retroviral therapy with potentially significant advantages over existing therapies. Xanthoviridicatins E (1) and F (2) ar ...
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Journal ArticleJ Am Soc Mass Spectrom · June 2003
Electron capture dissociation (ECD) and collision-induced dissociation (CID), the two complementary fragmentation techniques, are demonstrated to be effective in the detection and localization of the methionine sulfoxide [Met(O)] residues in peptides using ...
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Journal ArticleJ Ind Microbiol Biotechnol · April 2003
Mellamide, a novel indole amide, was isolated from a fermentation of Aspergillus melleus using silica gel and high-performance liquid chromatographic methods. This allowed its separation from three known antiparasitic compounds (ochratoxin A, viomellin and ...
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Journal ArticleJ Nat Prod · April 2003
HIV-1 integrase is a critical enzyme for replication of HIV, and its inhibition has the potential to lead to an anti-retroviral therapy that has advantages over existing therapies. Cytosporic acid (1) is a polyketide-derived novel natural product that was ...
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Journal ArticleRapid Commun Mass Spectrom · 2003
A potent and selective sulfonamide beta3 agonist with an excellent pharmacokinetic profile has recently been synthesized. During the analysis by liquid chromatography/tandem mass spectrometry (LC/MS/MS) of metabolites of the sulfonamide N-[4-[2-(2-hydroxy- ...
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Journal ArticleJ Am Soc Mass Spectrom · December 2002
Electron capture dissociation (ECD) has been demonstrated to be an effective fragmentation technique for characterizing the site and structure of the fatty acid modification in ghrelin, a 28-residue growth-hormone-releasing peptide that has an unusual este ...
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Journal ArticleProceedings 50th ASMS Conference on Mass Spectrometry and Allied Topics · December 1, 2002
The localization and characterization of peptide acylation with ester linkage by electron capture dissociation FTICR/MS were discussed. The electron capture dissociation (ECD) FTICR/MS were applied to ghrelin, a 28-residue acylated growth-hormone-releasing ...
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Journal ArticleJ Nat Prod · August 2002
Tat is a small HIV protein essential for both viral replication and the progression of HIV disease. In our efforts to discover Tat inhibitors from natural product screening of microbial fermentation extracts, we discovered durhamycin A (1) as a potent inhi ...
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Journal ArticleOrg Lett · May 2, 2002
[structure: see text]. Integramides A and B are two novel 16-mer linear peptides rich in C(alpha)-methyl amino acids that were isolated from fungal extracts of Dendrodochium sp. by employing a bioassay-guided isolation procedure using recombinant HIV-1 int ...
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Journal ArticleJournal of Molecular Catalysis - B Enzymatic · November 20, 2001
A panel of 27 commercial enzymes was screened for the deglycosylation of a triterpene glycoside (enfumafungin), an antifungal natural product with a novel mechanism of action that bears an ester, a hemi-acetal and a carboxylic acid functionalities in its s ...
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Journal ArticleJ Mass Spectrom · March 2001
In electrospray ionization (ESI) quadrupole ion trap and Fourier transform ion cyclotron resonance mass spectrometry, certain fragment ions (e.g. acylium ions) generated either during the ion transportation process (in the source interface region) or in th ...
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Journal ArticleTetrahedron Letters · November 4, 2000
The discovery, structure and absolute stereochemistry of coleophomones A and B are described, two structurally novel natural products that inhibit bacterial transglycosylase activity. Coleophomone A represents a new ring system, containing a highly condens ...
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Journal ArticleJournal of the American Chemical Society · May 20, 1998
Solution folding of a protein removes major sections of it from their aqueous environment. Complete removal, by forming water-free gaseous protein ions with electrospray ionization/mass spectrometry, profoundly changes the conformation of cytochrome c. Of ...
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Journal ArticleProc Natl Acad Sci U S A · March 31, 1998
Phenylglyoxal is an arginine-specific reagent that inactivates creatine kinase (CK). Previous results suggest that modification of the dimeric enzyme at a single arginine residue per subunit causes complete inactivation accompanied by the loss of nucleotid ...
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Journal ArticleInternational Journal of Mass Spectrometry and Ion Processes · January 1, 1997
As shown by Williams for positive multiply-charged ions, negative electrosprayed ions trapped in a Fourier-transform ion cyclotron resonance mass spectrometer can be dissociated efficiently with BIRD. For a 50-mer DNA, an ion cell wall temperature of 90°C ...
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Journal ArticleInternational Journal of Mass Spectrometry and Ion Processes · January 1, 1997
Electrospray ionization produces far more abundant molecular ions for double stranded (ds) DNA than for single stranded (ss) and accurate molecular masses can provide the base composition of dsDNA. This study shows that the Fourier-transform mass spectra o ...
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Journal ArticleJ Mass Spectrom · May 1996
For high-resolution Fourier transform mass spectrometry of electrosprayed proteins, the signal-to-noise ratio of measuring nozzle-skimmer fragment ions can be improved substantially by their broadband quadrupolar axialization (QA), even without increasing ...
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Journal ArticleInternational Journal of Mass Spectrometry and Ion Processes · January 1, 1996
In contrast to most ion dissociation methods, 193 nm ultraviolet photodissociation of electrosprayed melittin (2.8 kDa) and ubiquitin (8.6 kDa) molecular ions yields new c and z ions (backbone amine bond dissociation) that provide additional sequence infor ...
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Journal ArticleReview of Scientific Instruments · December 1, 1995
An improved, high-performance version of the concentric vacuum chamber design is shown for forming ions at high pressure in a strong magnetic field and detecting them in an adjacent Fourier transform ion cyclotron resonance mass spectrometry (FTICR) trappe ...
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Journal ArticleAnal Chem · April 15, 1995
A single population of multiply charged protein ions formed by electrospray ionization is held in a trapped ion cell and remeasured continuously by Fourier transform ion cyclotron resonance (FTICR) mass spectrometry while undergoing multiple reactions with ...
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Journal ArticleAnal Chem · January 15, 1995
Three cell geometries, closed cubic, closed elongated, and open elongated, are evaluated for optimum remeasurement performance in the Fourier transform ion cyclotron resonance mass spectrometry (FTICR) experiment. The advantages and disadvantages of each c ...
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Journal ArticleJournal of the American Society for Mass Spectrometry · January 1, 1995
The Fourier transform ion cyclotron resonance mass spectrometry remeasurement experiment is demonstrated and evaluated under high resolution conditions. Signal-to-noise enhancement is observed for isotopically resolved bovine insulin peaks at a resolution ...
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Journal ArticleJournal of Mass Spectrometry · January 1, 1995
Schiff‐bases formed by reaction between ketones and free amine sites in proteins yield mass‐shifted ions that are useful in assigning charge states in low resolution electrospray ionization mass spectra of mixtures and dissociation products. The technique ...
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Journal ArticleJournal of the American Society for Mass Spectrometry · January 1, 1994
Retarding grid and Fourier transform ion cyclotron resonance (FTICR) mass spectrometry variable trap potential measurements are performed to determine factors that contribute to the kinetic energy distribution of ions formed in an electrospray source that ...
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Journal ArticleAnal Chem · June 1, 1993
A single population of multiply charged protein ions formed by electrospray ionization (ESI) is subjected to multiple Fourier transform ion cyclotron resonance (FTICR) excitation and detection events without promoting ion loss from the trapped ion cell. Th ...
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Journal ArticleJournal of the American Society for Mass Spectrometry · January 1, 1993
A new differential pumping design for external source Fourier transform ion cyclotron resonance mass spectrometry is described. A network of concentric tubes of increasing diameter terminates at a series of conductance limits across which a pressure from a ...
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Journal ArticleJournal of Physical Chemistry · January 1, 1992
The incorporation of tetra-n-butylammonium (TBA+) upon electroreduction of films of C60 on an electrode in MeCN solutions was studied by electrochemical quartz crystal microbalance (EQCM) and laser desorption mass spectrometry (LDMS) methods. EQCM allowed ...
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