Catalytic Domain

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  Subject Areas on Research

  • 2.2 Å resolution cryo-EM structure of β-galactosidase in complex with a cell-permeant inhibitor. 
  • A Novel Phosphoregulatory Switch Controls the Activity and Function of the Major Catalytic Subunit of Protein Kinase A in Aspergillus fumigatus. 
  • A Sch9 protein kinase homologue controlling virulence independently of the cAMP pathway in Cryptococcus neoformans. 
  • A conserved domain for glycogen binding in protein phosphatase-1 targeting subunits. 
  • A conserved family of enzymes that phosphorylate inositol hexakisphosphate. 
  • A core-weighted fitting method for docking atomic structures into low-resolution maps: application to cryo-electron microscopy. 
  • A genetically tractable model of human glioma formation. 
  • A high affinity, antidote-controllable prothrombin and thrombin-binding RNA aptamer inhibits thrombin generation and thrombin activity. 
  • A protein encoded within the Down syndrome critical region is enriched in striated muscles and inhibits calcineurin signaling. 
  • A single step purification for autolytic zinc proteinases. 
  • Accurate Quantum Mechanical/Molecular Mechanical Calculations of Reduction Potentials in Azurin Variants. 
  • Activation of the abundant nuclear factor poly(ADP-ribose) polymerase-1 by Helicobacter pylori. 
  • Activity and stability of recombinant bifunctional rearranged and monofunctional domains of ATP-sulfurylase and adenosine 5'-phosphosulfate kinase. 
  • Allosteric effects of external K+ ions mediated by the aspartate of the GYGD signature sequence in the Kv2.1 K+ channel. 
  • Altered nucleotide-microtubule coupling and increased mechanical output by a kinesin mutant. 
  • Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing. 
  • Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase. 
  • Anti-inflammatory and vasoprotective activity of a retroviral-derived peptide, homologous to human endogenous retroviruses: endothelial cell effects. 
  • Automated image acquisition and processing using a new generation of 4K x 4K CCD cameras for cryo electron microscopic studies of macromolecular assemblies. 
  • BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. 
  • Branched-Chain Aminotransferases Control TORC1 Signaling in Saccharomyces cerevisiae. 
  • C-terminal regions of the human telomerase catalytic subunit essential for in vivo enzyme activity. 
  • Calcium Regulates the Activity and Structural Stability of Tpr, a Bacterial Calpain-like Peptidase. 
  • Cellular mechanisms regulating protein phosphatase-1. A key functional interaction between inhibitor-2 and the type 1 protein phosphatase catalytic subunit. 
  • Characterization of angiotensin-converting enzyme 2 ectodomain shedding from mouse proximal tubular cells. 
  • Characterization of key residues in the subdomain encoded by exons 8 and 9 of human inducible nitric oxide synthase: a critical role for Asp-280 in substrate binding and subunit interactions. 
  • Characterization of the CaMKKβ-AMPK signaling complex. 
  • Chlamydial CT441 is a PDZ domain-containing tail-specific protease that interferes with the NF-kappaB pathway of immune response. 
  • Choline Acetyltransferase Mutations Causing Congenital Myasthenic Syndrome: Molecular Findings and Genotype-Phenotype Correlations. 
  • Cloning and characterization of vmaA, the gene encoding a 69-kDa catalytic subunit of the vacuolar H+-ATPase during alkaline pH mediated growth of Aspergillus oryzae. 
  • Cloning and sequence analysis of cnaA gene encoding the catalytic subunit of calcineurin from Aspergillus oryzae. 
  • Computational design of a biologically active enzyme. 
  • Conformation-assisted inhibition of protein-tyrosine phosphatase-1B elicits inhibitor selectivity over T-cell protein-tyrosine phosphatase. 
  • Cryo-EM reveals active site coordination within a multienzyme pre-rRNA processing complex. 
  • Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis. 
  • Crystal structure of Streptococcus pyogenes sortase A: implications for sortase mechanism. 
  • Crystal structure of an efficacious gonococcal adherence inhibitor: an enolase from Lactobacillus gasseri. 
  • Crystal structure of the MOP flippase MurJ in an inward-facing conformation. 
  • Crystal structures of Ral-GppNHp and Ral-GDP reveal two binding sites that are also present in Ras and Rap. 
  • Crystal structures of the fungal pathogen Aspergillus fumigatus protein farnesyltransferase complexed with substrates and inhibitors reveal features for antifungal drug design. 
  • Cyclic AMP-dependent protein kinase catalytic subunits have divergent roles in virulence factor production in two varieties of the fungal pathogen Cryptococcus neoformans. 
  • Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans. 
  • Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae. 
  • Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation. 
  • Design, synthesis, and biologic evaluation of novel galloyl derivatives as HIV-1 RNase H inhibitors. 
  • Development of potent B-RafV600E inhibitors containing an arylsulfonamide headgroup. 
  • Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6. 
  • Direct evidence for methyl group coordination by carbon-oxygen hydrogen bonds in the lysine methyltransferase SET7/9. 
  • Directed evolution of a new catalytic site in 2-keto-3-deoxy-6-phosphogluconate aldolase from Escherichia coli. 
  • Divergence of protein kinase A catalytic subunits in Cryptococcus neoformans and Cryptococcus gattii illustrates evolutionary reconfiguration of a signaling cascade. 
  • Drosophila stretchin-MLCK is a novel member of the Titin/Myosin light chain kinase family. 
  • Dual-specific Cdc25B phosphatase: in search of the catalytic acid. 
  • Electrochemical cleavage of N=N bonds at a Mo2(mu-SMe)3 site relevant to the biological reduction of dinitrogen at a bimetallic sulfur centre. 
  • Emerging applications of aptamers for anticoagulation and hemostasis. 
  • Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase. 
  • Enzyme redesign guided by cancer-derived IDH1 mutations. 
  • Experimentally Dissecting the Origins of Peroxiredoxin Catalysis. 
  • From promiscuity to precision: protein phosphatases get a makeover. 
  • Heme-assisted S-nitrosation desensitizes ferric soluble guanylate cyclase to nitric oxide. 
  • High frequency of mutations of the PIK3CA gene in human cancers. 
  • HipBA-promoter structures reveal the basis of heritable multidrug tolerance. 
  • Human inter-α-inhibitor is a substrate for factor XIIIa and tissue transglutaminase. 
  • Hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition. 
  • IGFBP2 is overexpressed by pediatric malignant astrocytomas and induces the repair enzyme DNA-PK. 
  • Identification and characterization of a highly conserved calcineurin binding protein, CBP1/calcipressin, in Cryptococcus neoformans. 
  • Identification of casein kinase I substrates by in vitro expression cloning screening. 
  • Identification of cellular protein phosphatase-1 regulators. 
  • Identification of key amino acids responsible for the substantially higher affinities of human type 1 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD1) for substrates, coenzymes, and inhibitors relative to human 3beta-HSD2. 
  • Importance of a surface hydrophobic pocket on protein phosphatase-1 catalytic subunit in recognizing cellular regulators. 
  • Improving upon nature: active site remodeling produces highly efficient aldolase activity toward hydrophobic electrophilic substrates. 
  • Initiating cellular stress responses. 
  • Interplay of catalysis, fidelity, threading, and processivity in the exo- and endonucleolytic reactions of human exonuclease I. 
  • Involvement of the beta clamp in methyl-directed mismatch repair in vitro. 
  • Isocitrate-to-SENP1 signaling amplifies insulin secretion and rescues dysfunctional β cells. 
  • Maintenance of native-like protein dynamics may not be required for engineering functional proteins. 
  • Mapping hole hopping escape routes in proteins. 
  • Mcm2-7 Is an Active Player in the DNA Replication Checkpoint Signaling Cascade via Proposed Modulation of Its DNA Gate. 
  • Mechanism of OMP decarboxylation in orotidine 5'-monophosphate decarboxylase. 
  • Mechanistic analysis of the Saccharomyces cerevisiae kinesin Kar3. 
  • Miropin, a novel bacterial serpin from the periodontopathogen Tannerella forsythia, inhibits a broad range of proteases by using different peptide bonds within the reactive center loop. 
  • Molecular cloning and characterization of a novel histone deacetylase HDAC10. 
  • Molecular determinants of nuclear protein phosphatase-1 regulation by NIPP-1. 
  • Molecular mechanism of ERK dephosphorylation by striatal-enriched protein tyrosine phosphatase. 
  • Multiple interactions within the AKAP220 signaling complex contribute to protein phosphatase 1 regulation. 
  • Mutational analysis of active site residues in the Staphylococcus aureus transpeptidase SrtA. 
  • Mutational analysis of the tyrosine phosphatome in colorectal cancers. 
  • Mutations in hemG mediate resistance to salicylidene acylhydrazides, demonstrating a novel link between protoporphyrinogen oxidase (HemG) and Chlamydia trachomatis infectivity. 
  • N-terminal domains of the human telomerase catalytic subunit required for enzyme activity in vivo. 
  • NMR and XAS reveal an inner-sphere metal binding site in the P4 helix of the metallo-ribozyme ribonuclease P. 
  • Neurabins recruit protein phosphatase-1 and inhibitor-2 to the actin cytoskeleton. 
  • New mechanistic and functional insights into DNA topoisomerases. 
  • Novel motif in calcineurin catalytic subunit is required for septal localization of calcineurin in Aspergillus fumigatus. 
  • Nucleotide regulation of soluble guanylate cyclase substrate specificity. 
  • Oxidative stress-induced expression and modulation of Phosphatase of Regenerating Liver-1 (PRL-1) in mammalian retina. 
  • Perturbation of fuel homeostasis caused by overexpression of the glucose-6-phosphatase catalytic subunit in liver of normal rats. 
  • Phosphorylation of the myosin phosphatase target subunit by integrin-linked kinase. 
  • Photo-activated psoralen binds the ErbB2 catalytic kinase domain, blocking ErbB2 signaling and triggering tumor cell apoptosis. 
  • Potent anticoagulant aptamer directed against factor IXa blocks macromolecular substrate interaction. 
  • Probing domain interactions in soluble guanylate cyclase. 
  • Prolonged Adaptive Evolution of a Defensive Gene in the Solanaceae. 
  • Protein kinase A operates a molecular switch that governs yeast pseudohyphal differentiation. 
  • Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus. 
  • Protein serine/threonine phosphatases: life, death, and sleeping. 
  • Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4. 
  • Putative telomere-recruiting domain in the catalytic subunit of human telomerase. 
  • Reactive-site mutants of N-TIMP-3 that selectively inhibit ADAMTS-4 and ADAMTS-5: biological and structural implications. 
  • Results of allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia patients who failed tyrosine kinase inhibitors after developing BCR-ABL1 kinase domain mutations. 
  • Revisiting the steady state kinetic mechanism of glutamine-dependent asparagine synthetase from Escherichia coli. 
  • Separate and combined biochemical activities of the subunits of a naturally split reverse gyrase. 
  • Sirtuin 3 (SIRT3) protein regulates long-chain acyl-CoA dehydrogenase by deacetylating conserved lysines near the active site. 
  • Site-specific incorporation of 3-nitrotyrosine as a probe of pKa perturbation of redox-active tyrosines in ribonucleotide reductase. 
  • Small molecule-induced oxidation of protein disulfide isomerase is neuroprotective. 
  • Species-specific and inhibitor-dependent conformations of LpxC: implications for antibiotic design. 
  • Specific keynote: genome copy number abnormalities in ovarian cancer. 
  • Specificity determinants in phosphoinositide dephosphorylation: crystal structure of an archetypal inositol polyphosphate 5-phosphatase. 
  • Structural and In Vivo Studies on Trehalose-6-Phosphate Synthase from Pathogenic Fungi Provide Insights into Its Catalytic Mechanism, Biological Necessity, and Potential for Novel Antifungal Drug Design. 
  • Structural insights into inhibition of lipid I production in bacterial cell wall synthesis. 
  • Structural reorganization and preorganization in enzyme active sites: comparisons of experimental and theoretically ideal active site geometries in the multistep serine esterase reaction cycle. 
  • Structure of the LpxC deacetylase with a bound substrate-analog inhibitor. 
  • Structure of the manganese-bound manganese transport regulator of Bacillus subtilis. 
  • Structure of β-galactosidase at 3.2-Å resolution obtained by cryo-electron microscopy. 
  • Structure-based design and synthesis of potent, ethylenediamine-based, mammalian farnesyltransferase inhibitors as anticancer agents. 
  • Structures of Pathogenic Fungal FKBP12s Reveal Possible Self-Catalysis Function. 
  • Synthesis of programmable integrases. 
  • The Closing Mechanism of DNA Polymerase I at Atomic Resolution. 
  • The DNA binding domain of a papillomavirus E2 protein programs a chimeric nuclease to cleave integrated human papillomavirus DNA in HeLa cervical carcinoma cells. 
  • The Escherichia coli subtilase cytotoxin A subunit specifically cleaves cell-surface GRP78 protein and abolishes COOH-terminal-dependent signaling. 
  • The Hemophilus influenzae Hap autotransporter is a chymotrypsin clan serine protease and undergoes autoproteolysis via an intermolecular mechanism. 
  • The catalytic region and PEST domain of PTPN18 distinctly regulate the HER2 phosphorylation and ubiquitination barcodes. 
  • The catalytic subunits of IkappaB kinase, IKK-1 and IKK-2, contain non-equivalent active sites when expressed as homodimers. 
  • The cis-Pro touch-turn: a rare motif preferred at functional sites. 
  • The clash in titin. 
  • The crystal structure of the catalytic domain of a eukaryotic guanylate cyclase. 
  • The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization. 
  • The gain of rod phototransduction: reconciliation of biochemical and electrophysiological measurements. 
  • The hydrophilic, protease-sensitive terminal domains of eucaryotic DNA topoisomerases have essential intracellular functions. 
  • The mechanism of discrimination between oxidized and reduced coenzyme in the aldehyde dehydrogenase domain of Aldh1l1. 
  • The nucleolar localization domain of the catalytic subunit of human telomerase. 
  • The promoter for the gene encoding the catalytic subunit of rat glucose-6-phosphatase contains two distinct glucose-responsive regions. 
  • The structural basis for the selectivity of benzotriazole inhibitors of PTP1B. 
  • The structure of formylmethanofuran: tetrahydromethanopterin formyltransferase in complex with its coenzymes. 
  • The ubiquitin-conjugating enzyme (E2) Ube2w ubiquitinates the N terminus of substrates. 
  • beta-arrestin1 interacts with the catalytic domain of the tyrosine kinase c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in receptor endocytosis. 
  • c-Abl phosphorylates E6AP and regulates its E3 ubiquitin ligase activity. 
  • trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. 
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  Keywords of People

  • Berchuck, Andrew, James M. Ingram Distinguished Professor of Gynecologic Oncology, Obstetrics and Gynecology, Gynecologic Oncology
  • Erickson, Harold Paul, James B. Duke Distinguished Professor of Cell Biology, Biomedical Engineering
  • Sampson, John Howard, Robert H., M.D. and Gloria Wilkins Professor of Neurosurgery, in the School of Medicine, Immunology
  • Yan, Hai, Henry S. Friedman Distinguished Professor of Neuro-Oncology in the School of Medicine, Pathology