Scholars@Duke
Maria Anne Schumacher

Maria Anne Schumacher

Nanaline H. Duke Distinguished Professor of Biochemistry
Biochemistry
maria.schumacher@duke.edu
Box 3711, Durham, NC 27710
243A Nanaline H Duke, Durham, NC 27710

Selected Publications

How c-di-GMP controls progression through the Streptomyces life cycle.

Journal Article Curr Opin Microbiol · August 2024 Members of the antibiotic-producing bacterial genus Streptomyces undergo a complex developmental life cycle that culminates in the production of spores. Central to control of this cell differentiation process is signaling through the second messenger 3', 5 ... Full text Link to item Cite

Structure of the E. coli nucleoid-associated protein YejK reveals a novel DNA binding clamp.

Journal Article Nucleic Acids Res · July 8, 2024 Nucleoid-associated proteins (NAPs) play central roles in bacterial chromosome organization and DNA processes. The Escherichia coli YejK protein is a highly abundant, yet poorly understood NAP. YejK proteins are conserved among Gram-negative bacteria but s ... Full text Link to item Cite

Structure of the WYL-domain containing transcription activator, DriD, in complex with ssDNA effector and DNA target site.

Journal Article Nucleic Acids Res · February 9, 2024 Transcription regulators play central roles in orchestrating responses to changing environmental conditions. Recently the Caulobacter crescentus transcription activator DriD, which belongs to the newly defined WYL-domain family, was shown to regulate DNA d ... Full text Link to item Cite

Hormonal steroids induce multidrug resistance and stress response genes in Neisseria gonorrhoeae by binding to MtrR.

Journal Article Nat Commun · February 7, 2024 Transcriptional regulator MtrR inhibits the expression of the multidrug efflux pump operon mtrCDE in the pathogenic bacterium Neisseria gonorrhoeae. Here, we show that MtrR binds the hormonal steroids progesterone, β-estradiol, and testosterone, which are ... Full text Link to item Cite

M. mazei glutamine synthetase and glutamine synthetase-GlnK1 structures reveal enzyme regulation by oligomer modulation.

Journal Article Nat Commun · November 15, 2023 Glutamine synthetases (GS) play central roles in cellular nitrogen assimilation. Although GS active-site formation requires the oligomerization of just two GS subunits, all GS form large, multi-oligomeric machines. Here we describe a structural dissection ... Full text Link to item Cite

Structures of the DarR transcription regulator reveal unique modes of second messenger and DNA binding.

Journal Article Nat Commun · November 9, 2023 The mycobacterial repressor, DarR, a TetR family regulator (TFR), was the first transcription regulator shown to bind c-di-AMP. However, the molecular basis for this interaction and the mechanism involved in DNA binding by DarR remain unknown. Here we desc ... Full text Link to item Cite

Structure of the T. brucei kinetoplastid RNA editing substrate-binding complex core component, RESC5.

Journal Article PLoS One · 2023 Kinetoplastid protists such as Trypanosoma brucei undergo an unusual process of mitochondrial uridine (U) insertion and deletion editing termed kinetoplastid RNA editing (kRNA editing). This extensive form of editing, which is mediated by guide RNAs (gRNAs ... Full text Link to item Cite

Molecular Analysis of pSK1 par: A Novel Plasmid Partitioning System Encoded by Staphylococcal Multiresistance Plasmids.

Journal Article J Mol Biol · October 15, 2022 The segregation of prokaryotic plasmids typically requires a centromere-like site and two proteins, a centromere-binding protein (CBP) and an NTPase. By contrast, a single 245 residue Par protein mediates partition of the prototypical staphylococcal multir ... Full text Link to item Cite

Allosteric regulation of glycogen breakdown by the second messenger cyclic di-GMP.

Journal Article Nature communications · October 2022 Streptomyces are our principal source of antibiotics, which they generate concomitant with a complex developmental transition from vegetative hyphae to spores. c-di-GMP acts as a linchpin in this transition by binding and regulating the key developmental r ... Full text Cite

Molecular dissection of the glutamine synthetase-GlnR nitrogen regulatory circuitry in Gram-positive bacteria.

Journal Article Nat Commun · July 1, 2022 How bacteria sense and respond to nitrogen levels are central questions in microbial physiology. In Gram-positive bacteria, nitrogen homeostasis is controlled by an operon encoding glutamine synthetase (GS), a dodecameric machine that assimilates ammonium ... Full text Link to item Cite

ssDNA is an allosteric regulator of the C. crescentus SOS-independent DNA damage response transcription activator, DriD.

Journal Article Genes Dev · May 1, 2022 DNA damage repair systems are critical for genomic integrity. However, they must be coordinated with DNA replication and cell division to ensure accurate genomic transmission. In most bacteria, this coordination is mediated by the SOS response through LexA ... Full text Link to item Cite

Diverse molecular mechanisms of transcription regulation by the bacterial alarmone ppGpp.

Journal Article Mol Microbiol · February 2022 Bacteria must rapidly detect and respond to stressful environmental conditions. Guanosine tetraphosphate (ppGpp) is a universal stress signal that, in most bacteria, drives the reprograming of transcription at a global level. However, recent studies have r ... Full text Link to item Cite

The nucleotide messenger (p)ppGpp is an anti-inducer of the purine synthesis transcription regulator PurR in Bacillus.

Journal Article Nucleic Acids Res · January 25, 2022 The nucleotide messenger (p)ppGpp allows bacteria to adapt to fluctuating environments by reprogramming the transcriptome. Despite its well-recognized role in gene regulation, (p)ppGpp is only known to directly affect transcription in Proteobacteria by bin ... Full text Link to item Cite

Revealing A-T and G-C Hoogsteen base pairs in stressed protein-bound duplex DNA.

Journal Article Nucleic Acids Res · December 2, 2021 Watson-Crick base pairs (bps) are the fundamental unit of genetic information and the building blocks of the DNA double helix. However, A-T and G-C can also form alternative 'Hoogsteen' bps, expanding the functional complexity of DNA. We developed 'Hoog-fi ... Full text Link to item Cite

Evolution of a σ-(c-di-GMP)-anti-σ switch.

Journal Article Proc Natl Acad Sci U S A · July 27, 2021 Filamentous actinobacteria of the genus Streptomyces have a complex lifecycle involving the differentiation of reproductive aerial hyphae into spores. We recently showed c-di-GMP controls this transition by arming a unique anti-σ, RsiG, to bind the sporula ... Full text Link to item Cite

Structures of Neisseria gonorrhoeae MtrR-operator complexes reveal molecular mechanisms of DNA recognition and antibiotic resistance-conferring clinical mutations.

Journal Article Nucleic Acids Res · April 19, 2021 Mutations within the mtrR gene are commonly found amongst multidrug resistant clinical isolates of Neisseria gonorrhoeae, which has been labelled a superbug by the Centers for Disease Control and Prevention. These mutations appear to contribute to antibiot ... Full text Link to item Cite

Structural Basis for Virulence Activation of Francisella tularensis.

Journal Article Mol Cell · January 7, 2021 The bacterium Francisella tularensis (Ft) is one of the most infectious agents known. Ft virulence is controlled by a unique combination of transcription regulators: the MglA-SspA heterodimer, PigR, and the stress signal, ppGpp. MglA-SspA assembles with th ... Full text Link to item Cite

DNA mismatches reveal conformational penalties in protein-DNA recognition.

Journal Article Nature · November 2020 Transcription factors recognize specific genomic sequences to regulate complex gene-expression programs. Although it is well-established that transcription factors bind to specific DNA sequences using a combination of base readout and shape recognition, so ... Full text Open Access Cite

When is a transcription factor a NAP?

Journal Article Curr Opin Microbiol · June 2020 Proteins that regulate transcription often also play an architectural role in the genome. Thus, it has been difficult to define with precision the distinctions between transcription factors and nucleoid-associated proteins (NAPs). Anachronistic description ... Full text Link to item Cite

c-di-GMP Arms an Anti-σ to Control Progression of Multicellular Differentiation in Streptomyces.

Journal Article Mol Cell · February 6, 2020 Streptomyces are our primary source of antibiotics, produced concomitantly with the transition from vegetative growth to sporulation in a complex developmental life cycle. We previously showed that the signaling molecule c-di-GMP binds BldD, a master repre ... Full text Link to item Cite

High-resolution crystal structures of Escherichia coli FtsZ bound to GDP and GTP.

Journal Article Acta Crystallogr F Struct Biol Commun · February 1, 2020 Bacterial cytokinesis is mediated by the Z-ring, which is formed by the prokaryotic tubulin homolog FtsZ. Recent data indicate that the Z-ring is composed of small patches of FtsZ protofilaments that travel around the bacterial cell by treadmilling. Treadm ... Full text Open Access Link to item Cite

Structures of MERS1, the 5' processing enzyme of mitochondrial mRNAs in Trypanosoma brucei.

Journal Article RNA · January 2020 Most mitochondrial mRNAs are transcribed as polycistronic precursors that are cleaved by endonucleases to produce mature mRNA transcripts. However, recent studies have shown that mitochondrial transcripts in the kinetoplastid protozoan, Trypanosoma brucei, ... Full text Link to item Cite

Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents.

Journal Article Nat Commun · September 19, 2019 Calcineurin is important for fungal virulence and a potential antifungal target, but compounds targeting calcineurin, such as FK506, are immunosuppressive. Here we report the crystal structures of calcineurin catalytic (CnA) and regulatory (CnB) subunits c ... Full text Open Access Link to item Cite

Infrared Spectroscopic Observation of a G-C+ Hoogsteen Base Pair in the DNA:TATA-Box Binding Protein Complex Under Solution Conditions.

Journal Article Angew Chem Int Ed Engl · August 26, 2019 Hoogsteen DNA base pairs (bps) are an alternative base pairing to canonical Watson-Crick bps and are thought to play important biochemical roles. Hoogsteen bps have been reported in a handful of X-ray structures of protein-DNA complexes. However, there are ... Full text Open Access Link to item Cite

Structures of maintenance of carboxysome distribution Walker-box McdA and McdB adaptor homologs.

Journal Article Nucleic Acids Res · June 20, 2019 Carboxysomes, protein-coated organelles in cyanobacteria, are important in global carbon fixation. However, these organelles are present at low copy in each cell and hence must be segregated to ensure transmission from one generation to the next. Recent st ... Full text Link to item Cite

The RRM of the kRNA-editing protein TbRGG2 uses multiple surfaces to bind and remodel RNA.

Journal Article Nucleic Acids Res · February 28, 2019 Kinetoplastid RNA (kRNA) editing takes place in the mitochondria of kinetoplastid protists and creates translatable mRNAs by uridine insertion/deletion. Extensively edited (pan-edited) transcripts contain quadruplex forming guanine stretches, which must be ... Full text Link to item Cite

A Bacterial Chromosome Structuring Protein Binds Overtwisted DNA to Stimulate Type II Topoisomerases and Enable DNA Replication.

Journal Article Cell · October 4, 2018 When DNA is unwound during replication, it becomes overtwisted and forms positive supercoils in front of the translocating DNA polymerase. Unless removed or dissipated, this superhelical tension can impede replication elongation. Topoisomerases, including ... Full text Link to item Cite

The crystal structure of the RsbN-σBldN complex from Streptomyces venezuelae defines a new structural class of anti-σ factor.

Journal Article Nucleic Acids Res · August 21, 2018 Streptomyces are filamentous bacteria with a complex developmental life cycle characterized by the formation of spore-forming aerial hyphae. Transcription of the chaplin and rodlin genes, which are essential for aerial hyphae production, is directed by the ... Full text Link to item Cite

A potentially abundant junctional RNA motif stabilized by m6A and Mg2.

Journal Article Nat Commun · July 17, 2018 N6-Methyladenosine (m6A) is an abundant post-transcriptional RNA modification that influences multiple aspects of gene expression. In addition to recruiting proteins, m6A can modulate RNA function by destabilizing base pairing. Here, we show that when neig ... Full text Link to item Cite

Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.

Journal Article Proc Natl Acad Sci U S A · June 5, 2018 O-GlcNAc is an intracellular posttranslational modification that governs myriad cell biological processes and is dysregulated in human diseases. Despite this broad pathophysiological significance, the biochemical effects of most O-GlcNAcylation events rema ... Full text Open Access Link to item Cite

The MerR-like protein BldC binds DNA direct repeats as cooperative multimers to regulate Streptomyces development.

Journal Article Nat Commun · March 19, 2018 Streptomycetes are notable for their complex life cycle and production of most clinically important antibiotics. A key factor that controls entry into development and the onset of antibiotic production is the 68-residue protein, BldC. BldC is a putative DN ... Full text Link to item Cite

Dissection of the molecular circuitry controlling virulence in Francisella tularensis.

Journal Article Genes Dev · August 1, 2017 Francisella tularensis, the etiological agent of tularemia, is one of the most infectious bacteria known. Because of its extreme pathogenicity, F. tularensis is classified as a category A bioweapon by the US government. F. tularensis virulence stems from g ... Full text Link to item Cite

The Streptomyces master regulator BldD binds c-di-GMP sequentially to create a functional BldD2-(c-di-GMP)4 complex.

Journal Article Nucleic Acids Res · June 20, 2017 Streptomyces are ubiquitous soil bacteria that undergo a complex developmental transition coinciding with their production of antibiotics. This transition is controlled by binding of a novel tetrameric form of the second messenger, 3΄-5΄ cyclic diguanylic ... Full text Link to item Cite

A three-dimensional ParF meshwork assembles through the nucleoid to mediate plasmid segregation.

Journal Article Nucleic Acids Res · April 7, 2017 Genome segregation is a fundamental step in the life cycle of every cell. Most bacteria rely on dedicated DNA partition proteins to actively segregate chromosomes and low copy-number plasmids. Here, by employing super resolution microscopy, we establish th ... Full text Link to item Cite

Structure of the Z Ring-associated Protein, ZapD, Bound to the C-terminal Domain of the Tubulin-like Protein, FtsZ, Suggests Mechanism of Z Ring Stabilization through FtsZ Cross-linking.

Journal Article J Biol Chem · March 3, 2017 Cell division in most bacteria is mediated by the tubulin-like FtsZ protein, which polymerizes in a GTP-dependent manner to form the cytokinetic Z ring. A diverse repertoire of FtsZ-binding proteins affects FtsZ localization and polymerization to ensure co ... Full text Link to item Cite

Structures of partition protein ParA with nonspecific DNA and ParB effector reveal molecular insights into principles governing Walker-box DNA segregation.

Journal Article Genes Dev · March 1, 2017 Walker-box partition systems are ubiquitous in nature and mediate the segregation of bacterial and archaeal DNA. Well-studied plasmid Walker-box partition modules require ParA, centromere-DNA, and a centromere-binding protein, ParB. In these systems, ParA- ... Full text Link to item Cite

Bacterial Nucleoid Occlusion: Multiple Mechanisms for Preventing Chromosome Bisection During Cell Division.

Journal Article Subcell Biochem · 2017 In most bacteria cell division is driven by the prokaryotic tubulin homolog, FtsZ, which forms the cytokinetic Z ring. Cell survival demands both the spatial and temporal accuracy of this process to ensure that equal progeny are produced with intact genome ... Full text Link to item Cite

Structures of the activator of K. pneumonia biofilm formation, MrkH, indicates PilZ domains involved in c-di-GMP and DNA binding.

Journal Article Proc Natl Acad Sci U S A · September 6, 2016 The pathogenesis of Klebsiella pneumonia is linked to the bacteria's ability to form biofilms. Mannose-resistant Klebsiella-like (Mrk) hemagglutinins are critical for K pneumonia biofilm development, and the expression of the genes encoding these proteins ... Full text Link to item Cite

Molecular insights into DNA binding and anchoring by the Bacillus subtilis sporulation kinetochore-like RacA protein.

Journal Article Nucleic Acids Res · June 20, 2016 During Bacillus subtilis sporulation, segregating sister chromosomes are anchored to cell poles and the chromosome is remodeled into an elongated structure called the axial filament. Data indicate that a developmentally regulated protein called RacA is inv ... Full text Link to item Cite

Structures of the nucleoid occlusion protein SlmA bound to DNA and the C-terminal domain of the cytoskeletal protein FtsZ.

Journal Article Proc Natl Acad Sci U S A · May 3, 2016 Cell division in most prokaryotes is mediated by FtsZ, which polymerizes to create the cytokinetic Z ring. Multiple FtsZ-binding proteins regulate FtsZ polymerization to ensure the proper spatiotemporal formation of the Z ring at the division site. The DNA ... Full text Link to item Cite

Structures of Pathogenic Fungal FKBP12s Reveal Possible Self-Catalysis Function.

Journal Article mBio · April 26, 2016 UNLABELLED: Invasive fungal infections remain difficult to treat and require novel targeting strategies. The 12-kDa FK506-binding protein (FKBP12) is a ubiquitously expressed peptidyl-prolyl isomerase with considerable homology between fungal pathogens and ... Full text Link to item Cite

Structural and Functional Analyses Reveal Insights into the Molecular Properties of the Escherichia coli Z Ring Stabilizing Protein, ZapC.

Journal Article J Biol Chem · January 29, 2016 In Escherichia coli cell division is driven by the tubulin-like GTPase, FtsZ, which forms the cytokinetic Z-ring. The Z-ring serves as a dynamic platform for the assembly of the multiprotein divisome, which catalyzes membrane cleavage to create equal daugh ... Full text Link to item Cite

Structures of archaeal DNA segregation machinery reveal bacterial and eukaryotic linkages.

Journal Article Science · September 4, 2015 Although recent studies have provided a wealth of information about archaeal biology, nothing is known about the molecular basis of DNA segregation in these organisms. Here, we unveil the machinery and assembly mechanism of the archaeal Sulfolobus pNOB8 pa ... Full text Link to item Cite

Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host-pathogen interactions of the pathogenic mucoralean fungus Mucor circinelloides.

Journal Article Mol Microbiol · September 2015 Calcineurin plays essential roles in virulence and growth of pathogenic fungi and is a target of the natural products FK506 and Cyclosporine A. In the pathogenic mucoralean fungus Mucor circinelloides, calcineurin mutation or inhibition confers a yeast-loc ... Full text Link to item Cite

Structures of the T. brucei kRNA editing factor MRB1590 reveal unique RNA-binding pore motif contained within an ABC-ATPase fold.

Journal Article Nucleic Acids Res · August 18, 2015 Kinetoplastid RNA (kRNA) editing is a process that creates translatable mitochondrial mRNA transcripts from cryptogene encoded RNAs and is unique for kinetoplastids, such as Trypanosoma brucei. In addition to the catalytic 20S editosome, multiple accessory ... Full text Link to item Cite

HipBA-promoter structures reveal the basis of heritable multidrug tolerance.

Journal Article Nature · August 6, 2015 Multidrug tolerance is largely responsible for chronic infections and caused by a small population of dormant cells called persisters. Selection for survival in the presence of antibiotics produced the first genetic link to multidrug tolerance: a mutant in ... Full text Link to item Cite

Mechanism of pyranopterin ring formation in molybdenum cofactor biosynthesis.

Journal Article Proc Natl Acad Sci U S A · May 19, 2015 The molybdenum cofactor (Moco) is essential for all kingdoms of life, plays central roles in various biological processes, and must be biosynthesized de novo. During Moco biosynthesis, the characteristic pyranopterin ring is constructed by a complex rearra ... Full text Link to item Cite

Structures of regulatory machinery reveal novel molecular mechanisms controlling B. subtilis nitrogen homeostasis.

Journal Article Genes Dev · February 15, 2015 All cells must sense and adapt to changing nutrient availability. However, detailed molecular mechanisms coordinating such regulatory pathways remain poorly understood. In Bacillus subtilis, nitrogen homeostasis is controlled by a unique circuitry composed ... Full text Link to item Cite

Structural and Biochemical Characterization of the Francisella tularensis Pathogenicity Regulator, Macrophage Locus Protein A (MglA).

Journal Article PLoS One · 2015 Francisella tularensis is one of the most infectious bacteria known and is the etiologic agent of tularemia. Francisella virulence arises from a 33 kilobase (Kb) pathogenicity island (FPI) that is regulated by the macrophage locus protein A (MglA) and the ... Full text Link to item Cite

Structural basis of lipid binding for the membrane-embedded tetraacyldisaccharide-1-phosphate 4'-kinase LpxK.

Journal Article J Biol Chem · August 29, 2014 The membrane-bound tetraacyldisaccharide-1-phosphate 4'-kinase, LpxK, catalyzes the sixth step of the lipid A (Raetz) biosynthetic pathway and is a viable antibiotic target against emerging Gram-negative pathogens. We report the crystal structure of lipid ... Full text Link to item Cite

Tetrameric c-di-GMP mediates effective transcription factor dimerization to control Streptomyces development.

Journal Article Cell · August 28, 2014 The cyclic dinucleotide c-di-GMP is a signaling molecule with diverse functions in cellular physiology. Here, we report that c-di-GMP can assemble into a tetramer that mediates the effective dimerization of a transcription factor, BldD, which controls the ... Full text Link to item Cite

Mechanism of staphylococcal multiresistance plasmid replication origin assembly by the RepA protein.

Journal Article Proc Natl Acad Sci U S A · June 24, 2014 The staphylococcal multiresistance plasmids are key contributors to the alarming rise in bacterial multidrug resistance. A conserved replication initiator, RepA, encoded on these plasmids is essential for their propagation. RepA proteins consist of flexibl ... Full text Link to item Cite

Ligand concentration regulates the pathways of coupled protein folding and binding.

Journal Article J Am Chem Soc · January 22, 2014 Coupled ligand binding and conformational change plays a central role in biological regulation. Ligands often regulate protein function by modulating conformational dynamics, yet the order in which binding and conformational change occurs are often hotly d ... Full text Link to item Cite

Structures of the Bacillus subtilis glutamine synthetase dodecamer reveal large intersubunit catalytic conformational changes linked to a unique feedback inhibition mechanism.

Journal Article J Biol Chem · December 13, 2013 Glutamine synthetase (GS), which catalyzes the production of glutamine, plays essential roles in nitrogen metabolism. There are two main bacterial GS isoenzymes, GSI-α and GSI-β. GSI-α enzymes, which have not been structurally characterized, are uniquely f ... Full text Link to item Cite

The structure of irisin reveals a novel intersubunit β-sheet fibronectin type III (FNIII) dimer: implications for receptor activation.

Journal Article J Biol Chem · November 22, 2013 Irisin was recently identified as a putative myokine that is induced by exercise. Studies suggest that it is produced by cleavage of the FNDC5 (fibronectin domain-containing protein 5) receptor; irisin corresponds to the extracellular receptor ectodomain. ... Full text Open Access Link to item Cite

SlmA forms a higher-order structure on DNA that inhibits cytokinetic Z-ring formation over the nucleoid.

Journal Article Proc Natl Acad Sci U S A · June 25, 2013 The spatial and temporal control of Filamenting temperature sensitive mutant Z (FtsZ) Z-ring formation is crucial for proper cell division in bacteria. In Escherichia coli, the synthetic lethal with a defective Min system (SlmA) protein helps mediate nucle ... Full text Link to item Cite

Structures of the Escherichia coli transcription activator and regulator of diauxie, XylR: an AraC DNA-binding family member with a LacI/GalR ligand-binding domain.

Journal Article Nucleic Acids Res · February 1, 2013 Escherichia coli can rapidly switch to the metabolism of l-arabinose and d-xylose in the absence of its preferred carbon source, glucose, in a process called carbon catabolite repression. Transcription of the genes required for l-arabinose and d-xylose con ... Full text Link to item Cite

Uncoupling of nucleotide hydrolysis and polymerization in the ParA protein superfamily disrupts DNA segregation dynamics.

Journal Article J Biol Chem · December 14, 2012 DNA segregation in bacteria is mediated most frequently by proteins of the ParA superfamily that transport DNA molecules attached via the segrosome nucleoprotein complex. Segregation is governed by a cycle of ATP-induced polymerization and subsequent depol ... Full text Link to item Cite

Molecular basis for a protein-mediated DNA-bridging mechanism that functions in condensation of the E. coli chromosome.

Journal Article Mol Cell · November 30, 2012 The E. coli chromosome is condensed into insulated regions termed macrodomains (MDs), which are essential for genomic packaging. How chromosomal MDs are specifically organized and compacted is unknown. Here, we report studies revealing the molecular basis ... Full text Link to item Cite

Role of unusual P loop ejection and autophosphorylation in HipA-mediated persistence and multidrug tolerance.

Journal Article Cell 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 ... Full text Link to item Cite

Structural mechanism of ATP-induced polymerization of the partition factor ParF: implications for DNA segregation.

Journal Article J Biol Chem · July 27, 2012 Segregation of the bacterial multidrug resistance plasmid TP228 requires the centromere-binding protein ParG, the parH centromere, and the Walker box ATPase ParF. The cycling of ParF between ADP- and ATP-bound states drives TP228 partition; ATP binding sti ... Full text Link to item Cite

Bacterial plasmid partition machinery: a minimalist approach to survival.

Journal Article Curr Opin Struct Biol · February 2012 The accurate segregation or partition of replicated DNA is essential for ensuring stable genome transmission. Partition of bacterial plasmids requires only three elements: a centromere-like DNA site and two proteins, a partition NTPase, and a centromere-bi ... Full text Link to item Cite

Regulation of the Escherichia coli HipBA toxin-antitoxin system by proteolysis.

Journal Article PLoS One · 2012 Bacterial populations produce antibiotic-tolerant persister cells. A number of recent studies point to the involvement of toxin/antitoxin (TA) modules in persister formation. hipBA is a type II TA module that codes for the HipB antitoxin and the HipA toxin ... Full text Link to item Cite

The crystal structure of the TetR family transcriptional repressor SimR bound to DNA and the role of a flexible N-terminal extension in minor groove binding.

Journal Article Nucleic Acids Res · November 2011 SimR, a TetR-family transcriptional regulator (TFR), controls the export of simocyclinone, a potent DNA gyrase inhibitor made by Streptomyces antibioticus. Simocyclinone is exported by a specific efflux pump, SimX and the transcription of simX is repressed ... Full text Link to item Cite

Implications for proteasome nuclear localization revealed by the structure of the nuclear proteasome tether protein Cut8.

Journal Article Proc Natl Acad Sci U S A · October 11, 2011 Degradation of nuclear proteins by the 26S proteasome is essential for cell viability. In yeast, the nuclear envelope protein Cut8 mediates nuclear proteasomal sequestration by an uncharacterized mechanism. Here we describe structures of Schizosaccharomyce ... Full text Link to item Cite

Caspase-3 cleavage links delta-catenin to the novel nuclear protein ZIFCAT.

Journal Article J Biol Chem · July 1, 2011 δ-Catenin is an Armadillo protein of the p120-catenin subfamily capable of modulating cadherin stability, small GTPase activity, and nuclear transcription. From yeast two-hybrid screening of a human embryonic stem cell cDNA library, we identified δ-catenin ... Full text Link to item Cite

Structures of carbon catabolite protein A-(HPr-Ser46-P) bound to diverse catabolite response element sites reveal the basis for high-affinity binding to degenerate DNA operators.

Journal Article Nucleic Acids Res · April 2011 In Gram-positive bacteria, carbon catabolite protein A (CcpA) is the master regulator of carbon catabolite control, which ensures optimal energy usage under diverse conditions. Unlike other LacI-GalR proteins, CcpA is activated for DNA binding by first for ... Full text Link to item Cite

A single acidic residue can guide binding site selection but does not govern QacR cationic-drug affinity.

Journal Article PLoS One · January 17, 2011 Structures of the multidrug-binding repressor protein QacR with monovalent and bivalent cationic drugs revealed that the carboxylate side-chains of E90 and E120 were proximal to the positively charged nitrogens of the ligands ethidium, malachite green and ... Full text Link to item Cite

Molecular mechanism by which the nucleoid occlusion factor, SlmA, keeps cytokinesis in check.

Journal Article EMBO J · January 5, 2011 In Escherichia coli, cytokinesis is orchestrated by FtsZ, which forms a Z-ring to drive septation. Spatial and temporal control of Z-ring formation is achieved by the Min and nucleoid occlusion (NO) systems. Unlike the well-studied Min system, less is know ... Full text Link to item Cite

Insight into F plasmid DNA segregation revealed by structures of SopB and SopB-DNA complexes.

Journal Article Nucleic Acids Res · July 2010 Accurate DNA segregation is essential for genome transmission. Segregation of the prototypical F plasmid requires the centromere-binding protein SopB, the NTPase SopA and the sopC centromere. SopB displays an intriguing range of DNA-binding properties esse ... Full text Link to item Cite

Plasmid protein TubR uses a distinct mode of HTH-DNA binding and recruits the prokaryotic tubulin homolog TubZ to effect DNA partition.

Journal Article Proc Natl Acad Sci U S A · June 29, 2010 The segregation of plasmid DNA typically requires three elements: a DNA centromere site, an NTPase, and a centromere-binding protein. Because of their simplicity, plasmid partition systems represent tractable models to study the molecular basis of DNA segr ... Full text Link to item Cite

Structure of the Trypanosoma brucei p22 protein, a cytochrome oxidase subunit II-specific RNA-editing accessory factor.

Journal Article J Biol Chem · June 11, 2010 Kinetoplastid RNA (k-RNA) editing is a complex process in the mitochondria of kinetoplastid protozoa, including Trypanosoma brucei, that involves the guide RNA-directed insertion and deletion of uridines from precursor-mRNAs to produce mature, translatable ... Full text Link to item Cite

Structure and filament dynamics of the pSK41 actin-like ParM protein: implications for plasmid DNA segregation.

Journal Article J Biol Chem · March 26, 2010 Type II plasmid partition systems utilize ParM NTPases in coordination with a centromere-binding protein called ParR to mediate accurate DNA segregation, a process critical for plasmid retention. The Staphylococcus aureus pSK41 plasmid is a medically impor ... Full text Link to item Cite

The Staphylococcus aureus pSK41 plasmid-encoded ArtA protein is a master regulator of plasmid transmission genes and contains a RHH motif used in alternate DNA-binding modes.

Journal Article Nucleic Acids Res · November 2009 Plasmids harbored by Staphylococcus aureus are a major contributor to the spread of bacterial multi-drug resistance. Plasmid conjugation and partition are critical to the dissemination and inheritance of such plasmids. Here, we demonstrate that the ArtA pr ... Full text Link to item Cite

Structural basis for ADP-mediated transcriptional regulation by P1 and P7 ParA.

Journal Article EMBO J · June 17, 2009 The accurate segregation of DNA is essential for the faithful inheritance of genetic information. Segregation of the prototypical P1 plasmid par system requires two proteins, ParA and ParB, and a centromere. When bound to ATP, ParA mediates segregation by ... Full text Link to item Cite

Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB.

Journal Article Science · January 16, 2009 Bacterial multidrug tolerance is largely responsible for the inability of antibiotics to eradicate infections and is caused by a small population of dormant bacteria called persisters. HipA is a critical Escherichia coli persistence factor that is normally ... Full text Link to item Cite

Crystal structure of human type III collagen Gly991-Gly1032 cystine knot-containing peptide shows both 7/2 and 10/3 triple helical symmetries.

Journal Article J Biol Chem · November 21, 2008 Type III collagen is a critical collagen that comprises extensible connective tissue such as skin, lung, and the vascular system. Mutations in the type III collagen gene, COL3A1, are associated with the most severe forms of Ehlers-Danlos syndrome. A charac ... Full text Link to item Cite

QacR-cation recognition is mediated by a redundancy of residues capable of charge neutralization.

Journal Article Biochemistry · August 5, 2008 The Staphylococcus aureus multidrug binding protein QacR binds to a broad spectrum of structurally dissimilar cationic, lipophilic drugs. Our previous structural analyses suggested that five QacR glutamic acid residues are critical for charge neutralizatio ... Full text Link to item Cite

Structure and function of the native and recombinant mitochondrial MRP1/MRP2 complex from Trypanosoma brucei.

Journal Article Int J Parasitol · July 2008 The mitochondrial RNA-binding proteins (MRP) 1 and 2 play a regulatory role in RNA editing and putative role(s) in RNA processing in Trypanosoma brucei. Here, we report the purification of a high molecular weight protein complex consisting solely of the MR ... Full text Link to item Cite

Structural biology of plasmid partition: uncovering the molecular mechanisms of DNA segregation.

Journal Article Biochem J · May 15, 2008 DNA segregation or partition is an essential process that ensures stable genome transmission. In prokaryotes, partition is best understood for plasmids, which serve as tractable model systems to study the mechanistic underpinnings of DNA segregation at a d ... Full text Link to item Cite

Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression.

Journal Article Mol Cell Biol · March 2008 In hepatic cells, Smad and SnoN proteins converge with p53 to repress transcription of AFP, an oncodevelopmental tumor marker aberrantly reactivated in hepatoma cells. Using p53- and SnoN-depleted hepatoma cell clones, we define a mechanism for repression ... Full text Link to item Cite

Segrosome structure revealed by a complex of ParR with centromere DNA.

Journal Article Nature · December 20, 2007 The stable inheritance of genetic material depends on accurate DNA partition. Plasmids serve as tractable model systems to study DNA segregation because they require only a DNA centromere, a centromere-binding protein and a force-generating ATPase. The cen ... Full text Link to item Cite

Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose 6-phosphate and fructose 1,6-bisphosphate.

Journal Article J Mol Biol · May 11, 2007 In Gram-positive bacteria, carbon catabolite regulation (CCR) is mediated by the carbon catabolite control protein A (CcpA), a member of the LacI-GalR family of transcription regulators. Unlike other LacI-GalR proteins, CcpA is activated to bind DNA by bin ... Full text Link to item Cite

P1 partition complex assembly involves several modes of protein-DNA recognition.

Journal Article J Biol Chem · April 13, 2007 Assembly of P1 plasmid partition complexes at the partition site, parS, is nucleated by a dimer of P1 ParB and Escherichia coli integration host factor (IHF), which promotes loading of more ParB dimers and the pairing of plasmids during the cell cycle. Par ... Full text Link to item Cite

Structure of a four-way bridged ParB-DNA complex provides insight into P1 segrosome assembly.

Journal Article J Biol Chem · April 6, 2007 The plasmid partition process is essential for plasmid propagation and is mediated by par systems, consisting of centromere-like sites and two proteins, ParA and ParB. In the first step of partition by the archetypical P1 system, ParB binds a complicated c ... Full text Link to item Cite

Structural biology of plasmid segregation proteins.

Journal Article Curr Opin Struct Biol · February 2007 DNA segregation, or partition, ensures stable genome transmission during cell division. In prokaryotes, partition is best understood for plasmids, which serve as tractable model systems to decipher the molecular underpinnings of this process. Plasmid parti ... Full text Link to item Cite

The crystal structure of a collagen-like polypeptide with 3(S)-hydroxyproline residues in the Xaa position forms a standard 7/2 collagen triple helix.

Journal Article J Biol Chem · September 15, 2006 Collagen has a triple helical structure comprising strands with a repeating Xaa-Yaa-Gly sequence. L-Proline (Pro) and 4(R)-hydroxyl-L-proline (4(R)Hyp) residues are found most frequently in the Xaa and Yaa positions. However, in natural collagen, 3(S)-hydr ... Full text Link to item Cite

Crystal structures of T. brucei MRP1/MRP2 guide-RNA binding complex reveal RNA matchmaking mechanism.

Journal Article Cell · August 25, 2006 The mitochondrial RNA binding proteins MRP1 and MRP2 form a heteromeric complex that functions in kinetoplastid RNA editing. In this process, MRP1/MRP2 serves as a matchmaker by binding to guide RNAs and facilitating their hybridization with cognate preedi ... Full text Link to item Cite

Phosphoprotein Crh-Ser46-P displays altered binding to CcpA to effect carbon catabolite regulation.

Journal Article J Biol Chem · March 10, 2006 In Gram-positive bacteria, the catabolite control protein A (CcpA) functions as the master transcriptional regulator of carbon catabolite repression/regulation (CCR). To effect CCR, CcpA binds a phosphoprotein, either HPr-Ser46-P or Crh-Ser46-P. Although C ... Full text Link to item Cite

Structures of ParB bound to DNA reveal mechanism of partition complex formation.

Journal Article Nature · November 24, 2005 The faithful inheritance of genetic information, which is essential for all organisms, requires accurate DNA partition (segregation) at cell division. In prokaryotes, partition is mediated by par systems, for which the P1 plasmid system of Escherichia coli ... Full text Link to item Cite

The crystal structure of the collagen-like polypeptide (glycyl-4(R)-hydroxyprolyl-4(R)-hydroxyprolyl)9 at 1.55 A resolution shows up-puckering of the proline ring in the Xaa position.

Journal Article J Biol Chem · May 27, 2005 The collagen triple helix is characterized by the repeating sequence motif Gly-Xaa-Yaa, where Xaa and Yaa are typically proline and (2S,4R)-4-hydroxyproline (4(R)Hyp), respectively. Previous analyses have revealed that H-(Pro-4(R)Hyp-Gly)(10)-OH forms a st ... Full text Link to item Cite

Structural basis for allosteric control of the transcription regulator CcpA by the phosphoprotein HPr-Ser46-P.

Journal Article Cell · September 17, 2004 Carbon catabolite repression (CCR) is one of the most fundamental environmental-sensing mechanisms in bacteria and imparts competitive advantage by establishing priorities in carbon metabolism. In gram-positive bacteria, the master transcription regulator ... Full text Link to item Cite

Structural mechanism of the simultaneous binding of two drugs to a multidrug-binding protein.

Journal Article EMBO J · August 4, 2004 The structural basis of simultaneous binding of two or more different drugs by any multidrug-binding protein is unknown and also how this can lead to a noncompetitive, uncompetitive or cooperative binding mechanism. Here, we describe the crystal structure ... Full text Link to item Cite

Crystal structures of apocalmodulin and an apocalmodulin/SK potassium channel gating domain complex.

Journal Article Structure · May 2004 Small conductance Ca2+-activated K+ channels (SK channels) are composed of the pore-forming alpha subunit and calmodulin (CaM). CaM binds to a region of the alpha subunit called the CaM binding domain (CaMBD), located intracellular and immediately C-termin ... Full text Link to item Cite

Crystal structures of QacR-diamidine complexes reveal additional multidrug-binding modes and a novel mechanism of drug charge neutralization.

Journal Article J Biol Chem · April 2, 2004 The Staphylococcus aureus multidrug-binding protein QacR represses transcription of the plasmid-encoded membrane protein QacA, a multidrug efflux transporter. QacR is induced by multiple structurally dissimilar monovalent and bivalent cationic lipophilic c ... Full text Link to item Cite

Structural basis of core promoter recognition in a primitive eukaryote.

Journal Article Cell · November 14, 2003 Transcription start site selection in eukaryotes is mediated through combinations of the TATA, initiator (Inr), and downstream promoter elements (DPE). In Trichomonas vaginalis, a parabasalian flagellate thought to represent an ancient eukaryote lineage, t ... Full text Link to item Cite

Deciphering the molecular basis of multidrug recognition: crystal structures of the Staphylococcus aureus multidrug binding transcription regulator QacR.

Journal Article Res Microbiol · March 2003 Multidrug transporters and their transcriptional regulators are key components of bacterial multidrug resistance (MDR). How these multidrug binding proteins can recognize such chemically disparate compounds represents a fascinating question from a structur ... Full text Link to item Cite

Structural mechanisms of multidrug recognition and regulation by bacterial multidrug transcription factors.

Journal Article Mol Microbiol · August 2002 The increase in bacterial resistance to multiple drugs represents a serious and growing health risk. One component of multidrug resistance (MDR) is a group of multidrug transporters that are often regulated at the transcriptional level by repressors and/or ... Full text Link to item Cite

Localization of the activation gate for small conductance Ca2+-activated K+ channels.

Journal Article J Neurosci · August 1, 2002 Small conductance Ca2+-activated K+ (SK) channels open in response to increased cytosolic Ca2+ and contribute to the afterhyperpolarization in many excitable cell types. Opening of SK channels is initiated by Ca2+ binding to calmodulin that is bound to the ... Full text Link to item Cite

Structures of the pleiotropic translational regulator Hfq and an Hfq-RNA complex: a bacterial Sm-like protein.

Journal Article EMBO J · July 1, 2002 In prokaryotes, Hfq regulates translation by modulating the structure of numerous RNA molecules by binding preferentially to A/U-rich sequences. To elucidate the mechanisms of target recognition and translation regulation by Hfq, we determined the crystal ... Full text Link to item Cite

Ion channels: an open and shut case.

Journal Article Nature · May 30, 2002 Full text Link to item Cite

Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase.

Journal Article Biochemistry · March 5, 2002 Human VHR (vaccinia H1 related phosphatase) is a member of the dual-specificity phosphatases (DSPs) that often act on bisphosphorylated protein substrates. Unlike most DSPs, VHR displays a strong preference for dephosphorylating phosphotyrosine residues ov ... Full text Link to item Cite

Structural basis for cooperative DNA binding by two dimers of the multidrug-binding protein QacR.

Journal Article EMBO J · March 1, 2002 The Staphylococcus aureus multidrug-binding protein QacR represses transcription of the qacA multidrug transporter gene and is induced by multiple structurally dissimilar drugs. QacR is a member of the TetR/CamR family of transcriptional regulators, which ... Full text Link to item Cite

The structural mechanism of GTP stabilized oligomerization and catalytic activation of the Toxoplasma gondii uracil phosphoribosyltransferase.

Journal Article Proc Natl Acad Sci U S A · January 8, 2002 Uracil phosphoribosyltransferase (UPRT) is a member of a large family of salvage and biosynthetic enzymes, the phosphoribosyltransferases, and catalyzes the transfer of ribose 5-phosphate from alpha-d-5-phosphoribosyl-1-pyrophosphate (PRPP) to the N1 nitro ... Full text Link to item Cite

Structural mechanisms of QacR induction and multidrug recognition.

Journal Article Science · December 7, 2001 The Staphylococcus aureus multidrug binding protein QacR represses transcription of the qacA multidrug transporter gene and is induced by structurally diverse cationic lipophilic drugs. Here, we report the crystal structures of six QacR-drug complexes. Com ... Full text Link to item Cite

The staphylococcal QacR multidrug regulator binds a correctly spaced operator as a pair of dimers.

Journal Article J Bacteriol · December 2001 Expression of the Staphylococcus aureus plasmid-encoded QacA multidrug transporter is regulated by the divergently encoded QacR repressor protein. To circumvent the formation of disulfide-bonded degradation products, site-directed mutagenesis to replace th ... Full text Link to item Cite

Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin.

Journal Article Nature · April 26, 2001 Small-conductance Ca2+-activated K+ channels (SK channels) are independent of voltage and gated solely by intracellular Ca2+. These membrane channels are heteromeric complexes that comprise pore-forming alpha-subunits and the Ca2+-binding protein calmoduli ... Full text Link to item Cite

Consensus and variant cAMP-regulated enhancers have distinct CREB-binding properties.

Journal Article J Biol Chem · April 13, 2001 Recent determination of the cAMP response element-binding protein (CREB) basic leucine zipper (bZIP) consensus CRE crystal structure revealed key dimerization and DNA binding features that are conserved among members of the CREB/CREM/ATF-1 family of transc ... Full text Link to item Cite

Crystal structures of SarA, a pleiotropic regulator of virulence genes in S. aureus.

Journal Article Nature · January 11, 2001 Staphylococcus aureus is a major human pathogen, the potency of which can be attributed to the regulated expression of an impressive array of virulence determinants. A key pleiotropic transcriptional regulator of these virulence factors is SarA, which is e ... Full text Link to item Cite

The structure of a CREB bZIP.somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding.

Journal Article J Biol Chem · November 10, 2000 The cAMP responsive element-binding protein (CREB) is central to second messenger regulated transcription. To elucidate the structural mechanisms of DNA binding and selective dimerization of CREB, we determined to 3.0 A resolution, the structure of the CRE ... Full text Link to item Cite

The structural basis of repertoire shift in an immune response to phosphocholine.

Journal Article J Exp Med · June 19, 2000 The immune response to phosphocholine (PC)-protein is characterized by a shift in antibody repertoire as the response progresses. This change in expressed gene combinations is accompanied by a shift in fine specificity toward the carrier, resulting in high ... Full text Link to item Cite

Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.

Journal Article J Mol Biol · May 19, 2000 Adenosine kinase (AK) is a key purine metabolic enzyme from the opportunistic parasitic protozoan Toxoplasma gondii and belongs to the family of carbohydrate kinases that includes ribokinase. To understand the catalytic mechanism of AK, we determined the s ... Full text Link to item Cite

Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.

Journal Article J Mol Biol · February 18, 2000 Adenosine kinase (AK) is a key purine metabolic enzyme from the opportunistic parasitic protozoan Toxoplasma gondii and belongs to the family of carbohydrate kinases that includes ribokinase. To understand the catalytic mechanism of AK, we determined the s ... Full text Link to item Cite

The role of lysine 55 in determining the specificity of the purine repressor for its operators through minor groove interactions.

Journal Article J Mol Biol · August 13, 1999 The interaction of the dimeric Escherichia coli purine repressor (PurR) with its cognate sequences leads to a 45 degrees to 50 degrees kink at a central CpG base step towards the major groove, as dyad-related leucine side-chains interdigitate between these ... Full text Link to item Cite

Characterization of the SarA virulence gene regulator of Staphylococcus aureus.

Journal Article Mol Microbiol · July 1999 Staphylococcus aureus is a potent human pathogen that expresses a large number of virulence factors in a temporally regulated fashion. Two pleiotropically acting regulatory loci were identified in previous mutational studies. The agr locus comprises two op ... Full text Link to item Cite

Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding.

Journal Article EMBO J · June 15, 1998 Uracil phosphoribosyltransferase (UPRTase) catalyzes the transfer of a ribosyl phosphate group from alpha-D-5-phosphoribosyl-1-pyrophosphate to the N1 nitrogen of uracil. The UPRTase from the opportunistic pathogen Toxoplasma gondii is a rational target fo ... Full text Link to item Cite

Structure-based redesign of corepressor specificity of the Escherichia coli purine repressor by substitution of residue 190.

Journal Article Biochemistry · January 27, 1998 Guanine or hypoxanthine, physiological corepressors of the Escherichia coli purine repressor (PurR), promote formation of the ternary PurR-corepressor-operator DNA complex that functions to repress pur operon gene expression. Structure-based predictions on ... Full text Link to item Cite

The X-ray structure of the PurR-guanine-purF operator complex reveals the contributions of complementary electrostatic surfaces and a water-mediated hydrogen bond to corepressor specificity and binding affinity.

Journal Article J Biol Chem · September 5, 1997 The purine repressor, PurR, is the master regulatory protein of de novo purine nucleotide biosynthesis in Escherichia coli. This dimeric transcription factor is activated to bind to cognate DNA operator sites by initially binding either of its physiologica ... Full text Link to item Cite

Allosteric intermediates indicate R2 is the liganded hemoglobin end state.

Journal Article Proc Natl Acad Sci U S A · July 22, 1997 Hemoglobin has been a long-standing paradigm for understanding protein allostery. Here, the x-ray structures of two chemically crosslinked, fully liganded hemoglobins, alpha2beta82CA82beta and alpha2beta82ND82beta, are described at 2.3 A and 2.6 A resoluti ... Full text Link to item Cite

A positively charged residue bound in the minor groove does not alter the bending of a DNA duplex

Journal Article Journal of the American Chemical Society · December 25, 1996 Full text Cite

Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop.

Journal Article Nat Struct Biol · October 1996 Crystal structures of substrate-free and XMP-soaked hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase) of the opportunistic pathogen Toxoplasma gondii have been determined to 2.4 and 2.9 A resolution, respectively. HGXPRTase displays the c ... Full text Link to item Cite

Crystal structure of the lactose operon repressor and its complexes with DNA and inducer.

Journal Article Science · March 1, 1996 The lac operon of Escherichia coli is the paradigm for gene regulation. Its key component is the lac repressor, a product of the lacI gene. The three-dimensional structures of the intact lac repressor, the lac repressor bound to the gratuitous inducer isop ... Full text Link to item Cite

Structural comparison of the free and DNA-bound forms of the purine repressor DNA-binding domain.

Journal Article Structure · November 15, 1995 BACKGROUND: The purine repressor (PurR) regulates genes that encode enzymes for purine biosynthesis. PurR has a two domain structure with an N-terminal DNA-binding domain (DBD) and a C-terminal corepressor-binding domain (CBD). The three dimensional struct ... Full text Link to item Cite

Mechanism of corepressor-mediated specific DNA binding by the purine repressor.

Journal Article Cell · October 6, 1995 The modulation of the affinity of DNA-binding proteins by small molecule effectors for cognate DNA sites is common to both prokaryotes and eukaryotes. However, the mechanisms by which effector binding to one domain affects DNA binding by a distal domain ar ... Full text Link to item Cite

Allosteric transition intermediates modelled by crosslinked haemoglobins.

Journal Article Nature · May 4, 1995 The structural end-points of haemoglobin's transition from its low-oxygen-affinity (T) to high-oxygen-affinity (R) state, have been well established by X-ray crystallography, but short-lived intermediates have proved less amenable to X-ray studies. Here we ... Full text Link to item Cite

Conformational changes of purine repressor DNA-binding domain upon complexation with DNA.

Journal Article Nucleic Acids Symp Ser · 1995 The purine repressor (PurR) consists of two functional domains: an N-terminal DNA-binding domain and a C-terminal corepressor-binding domain. Recently, the structure of PurR-corepressor-operator ternary complex was determined by X-ray crystallography. In t ... Link to item Cite

Crystal structure of LacI member, PurR, bound to DNA: minor groove binding by alpha helices.

Journal Article Science · November 4, 1994 The three-dimensional structure of a ternary complex of the purine repressor, PurR, bound to both its corepressor, hypoxanthine, and the 16-base pair purF operator site has been solved at 2.7 A resolution by x-ray crystallography. The bipartite structure o ... Full text Link to item Cite

Crystallization and preliminary X-ray analysis of an Escherichia coli purine repressor-hypoxanthine-DNA complex.

Journal Article J Mol Biol · September 23, 1994 The purine repressor (PurR) is a DNA-binding protein, which together with a purine corepressor serves to regulate de novo purine and pyrimidine biosynthesis in Escherichia coli. PurR belongs to the structurally homologous lac repressor family of transcript ... Full text Link to item Cite

Structural analysis of the purine repressor, an Escherichia coli DNA-binding protein.

Journal Article J Biol Chem · June 15, 1993 The purine repressor protein, PurR, is a member of the lac repressor, LacI, family of Escherichia coli DNA-binding proteins that bind DNA via a highly conserved N-terminal helix-turn-helix motif. Additionally, the members of this family display strong sequ ... Link to item Cite

Crystallization and preliminary X-ray studies on the co-repressor binding domain of the Escherichia coli purine repressor.

Journal Article J Mol Biol · June 20, 1992 The purine repressor is a putative helix-turn-helix DNA-binding protein that regulates several genetic loci important in purine and pyrimidine metabolism in Escherichia coli. The protein is composed of two domains, an N-terminal DNA-binding domain and a C- ... Full text Link to item Cite