catalytic domain

Summary

Summary: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.

Top Publications

  1. ncbi The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit
    Alexandre Dias
    Unit of Virus Host Cell Interactions, UJF EMBL CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
    Nature 458:914-8. 2009
  2. pmc Retroviral intasome assembly and inhibition of DNA strand transfer
    Stephen Hare
    Division of Medicine, Imperial College London, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Nature 464:232-6. 2010
  3. ncbi Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis
    Marcin Nowotny
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 121:1005-16. 2005
  4. ncbi Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site
    Puwei Yuan
    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
    Nature 458:909-13. 2009
  5. ncbi Mechanisms of site-specific recombination
    Nigel D F Grindley
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8114, USA
    Annu Rev Biochem 75:567-605. 2006
  6. ncbi Crystal structure of a bacterial RNA polymerase holoenzyme at 2.6 A resolution
    Dmitry G Vassylyev
    Cellular Signaling Laboratory, RIKEN Harima Institute at SPring 8, 1 1 1 Kouto, Mikazuki cho, Sayo, Hyogo 679 5148, Japan
    Nature 417:712-9. 2002
  7. ncbi Enzyme promiscuity: a mechanistic and evolutionary perspective
    Olga Khersonsky
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Annu Rev Biochem 79:471-505. 2010
  8. pmc The catalytic domain of all eukaryotic cut-and-paste transposase superfamilies
    Yao Wu Yuan
    Department of Plant Biology, University of Georgia, Athens, GA 30602, USA
    Proc Natl Acad Sci U S A 108:7884-9. 2011
  9. ncbi Structural insights into histone demethylation by JMJD2 family members
    Zhongzhou Chen
    Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA
    Cell 125:691-702. 2006
  10. pmc Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes
    Yanli Wang
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 461:754-61. 2009

Detail Information

Publications376 found, 100 shown here

  1. ncbi The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit
    Alexandre Dias
    Unit of Virus Host Cell Interactions, UJF EMBL CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
    Nature 458:914-8. 2009
    ..These results will facilitate the optimisation of endonuclease inhibitors as potential new anti-influenza drugs...
  2. pmc Retroviral intasome assembly and inhibition of DNA strand transfer
    Stephen Hare
    Division of Medicine, Imperial College London, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Nature 464:232-6. 2010
    ..Our findings define the structural basis of retroviral DNA integration, and will allow modelling of the HIV-1 intasome to aid in the development of antiretroviral drugs...
  3. ncbi Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis
    Marcin Nowotny
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 121:1005-16. 2005
    ..In transposases, they are symmetrically coordinated and exchange roles to alternately activate a water and a 3'-OH for successive strand cleavage and transfer by a ping-pong mechanism...
  4. ncbi Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site
    Puwei Yuan
    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
    Nature 458:909-13. 2009
    ..The high conservation of this endonuclease active site among influenza strains indicates that PA(N) is an important target for the design of new anti-influenza therapeutics...
  5. ncbi Mechanisms of site-specific recombination
    Nigel D F Grindley
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8114, USA
    Annu Rev Biochem 75:567-605. 2006
    ..Details of the site-specific recombination processes have been revealed by recent structural and biochemical studies of members of both families...
  6. ncbi Crystal structure of a bacterial RNA polymerase holoenzyme at 2.6 A resolution
    Dmitry G Vassylyev
    Cellular Signaling Laboratory, RIKEN Harima Institute at SPring 8, 1 1 1 Kouto, Mikazuki cho, Sayo, Hyogo 679 5148, Japan
    Nature 417:712-9. 2002
    ..The holoenzyme structure provides insight into the structural organization of transcription intermediate complexes and into the mechanism of transcription initiation...
  7. ncbi Enzyme promiscuity: a mechanistic and evolutionary perspective
    Olga Khersonsky
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Annu Rev Biochem 79:471-505. 2010
    ..Finally, we address the hypothesis that promiscuous enzymatic activities serve as evolutionary starting points and highlight the unique evolutionary features of promiscuous enzyme functions...
  8. pmc The catalytic domain of all eukaryotic cut-and-paste transposase superfamilies
    Yao Wu Yuan
    Department of Plant Biology, University of Georgia, Athens, GA 30602, USA
    Proc Natl Acad Sci U S A 108:7884-9. 2011
    ....
  9. ncbi Structural insights into histone demethylation by JMJD2 family members
    Zhongzhou Chen
    Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA
    Cell 125:691-702. 2006
    ..Sited-directed mutagenesis in conjunction with demethylase activity assays allowed us to propose a molecular model for substrate selection by the JMJD2 histone demethylase family...
  10. pmc Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes
    Yanli Wang
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 461:754-61. 2009
    ..Cleavage assays on targets of various lengths supported this model, and sugar-phosphate-backbone-modified target strands showed the importance of structural and catalytic divalent metal ions observed in the crystal structures...
  11. ncbi An RNA-induced conformational change required for CRISPR RNA cleavage by the endoribonuclease Cse3
    Dipali G Sashital
    Department of Molecular and Cell Biology, University of California, Berkeley, California, USA
    Nat Struct Mol Biol 18:680-7. 2011
    ..These studies provide insight into a catalytically essential RNA recognition mechanism by a large class of CRISPR-related endoRNases...
  12. pmc Structure and mechanism of human DNA polymerase eta
    Christian Biertümpfel
    Laboratory of Molecular Biology, NIDDK, NIH, 9000 Rockville Pike, Building 5, Room B103, Bethesda, Maryland 20892, USA
    Nature 465:1044-8. 2010
    ..The structures also provide an insight into the role of Poleta in replicating through D loop and DNA fragile sites...
  13. ncbi The structural basis of mode of activation and functional diversity: a case study with HtrA family of serine proteases
    Nitu Singh
    Advanced Centre for Treatment, Research and Education in Cancer ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, India
    Arch Biochem Biophys 516:85-96. 2011
    ....
  14. pmc Predicting protein ligand binding sites by combining evolutionary sequence conservation and 3D structure
    John A Capra
    Department of Computer Science, Princeton University, Princeton, New Jersey, United States of America
    PLoS Comput Biol 5:e1000585. 2009
    ..Data, source code, and prediction visualizations are available on the ConCavity web site (http://compbio.cs.princeton.edu/concavity/)...
  15. ncbi Protein dynamism and evolvability
    Nobuhiko Tokuriki
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Science 324:203-7. 2009
    ..This dynamic view of protein structure, function, and evolvability is extrapolated to describe hypothetical scenarios for the evolution of the early proteins and future research directions in the area of protein dynamism and evolution...
  16. ncbi Structure of human RNase H1 complexed with an RNA/DNA hybrid: insight into HIV reverse transcription
    Marcin Nowotny
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 28:264-76. 2007
    ..The region that accommodates this conformational change offers a target to develop HIV-specific inhibitors...
  17. ncbi Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade
    L Huang
    Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Science 286:1321-6. 1999
    ..The crystal structure of the E6AP hect domain bound to the UbcH7 ubiquitin-conjugating enzyme (E2) reveals the determinants of E2-E3 specificity and provides insights into the transfer of ubiquitin from the E2 to the E3...
  18. ncbi Mechanistic evidence for a front-side, SNi-type reaction in a retaining glycosyltransferase
    Seung Seo Lee
    Department of Chemistry, University of Oxford, Oxford, United Kingdom
    Nat Chem Biol 7:631-8. 2011
    ..Together, these comprehensive, quantitative data substantiate this unusual enzymatic reaction mechanism. Its discovery should prompt useful reassessment of many biocatalysts and their substrates and inhibitors...
  19. pmc Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex
    Hari B Kamadurai
    Department of Structural Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Mol Cell 36:1095-102. 2009
    ..The structure suggests a model for E2-to-HECT Ub transfer, in which interactions between a donor Ub and an acceptor domain constrain upstream and downstream enzymes for conjugation...
  20. pmc Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-angstrom resolution
    Thai Leong Yap
    Novartis Institute for Tropical Diseases, 05 01 Chromos, 10 Biopolis Road, Singapore 138670, Singapore
    J Virol 81:4753-65. 2007
    ..resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA ..
  21. pmc Directed evolution of an enhanced and highly efficient FokI cleavage domain for zinc finger nucleases
    Jing Guo
    The Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Mol Biol 400:96-107. 2010
    ..This enhanced and highly efficient cleavage domain will aid in a variety of ZFN applications in medicine and biology...
  22. ncbi Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins
    Yongna Xing
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, NJ 08544, USA
    Cell 127:341-53. 2006
    ..These structures, together with biochemical analyses, reveal significant insights into PP2A function and serve as a framework for deciphering the diverse roles of PP2A in cellular physiology...
  23. ncbi Crystal structure of a self-spliced group II intron
    Navtej Toor
    Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, Bass Building, New Haven, CT 06511, USA
    Science 320:77-82. 2008
    ..interactions facilitates the ordered packing of intron subdomains around a ribozyme core that includes catalytic domain V...
  24. ncbi Structural basis for the requirement of additional factors for MLL1 SET domain activity and recognition of epigenetic marks
    Stacey M Southall
    Institute of Cancer Research, Chester Beatty Laboratories, Chelsea, London, UK
    Mol Cell 33:181-91. 2009
    ....
  25. pmc Unlocking the sugar "steric gate" of DNA polymerases
    Jessica A Brown
    Department of Biochemistry, Ohio State University, Columbus, Ohio 43210, United States
    Biochemistry 50:1135-42. 2011
    ..These important findings are summarized in this review...
  26. pmc Protein kinase CK2: structure, regulation and role in cellular decisions of life and death
    David W Litchfield
    Department of Biochemistry, Siebens Drake Research Institute, University of Western Ontario, London, Ontario, Canada N6A 5C1
    Biochem J 369:1-15. 2003
    ..Furthermore, this anti-apoptotic function of CK2 may contribute to its ability to participate in transformation and tumorigenesis...
  27. pmc Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction
    Justin B Siegel
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Science 329:309-13. 2010
    ..Designed stereoselective catalysts for carbon-carbon bond-forming reactions should be broadly useful in synthetic chemistry...
  28. pmc Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases
    Giorgio Giardina
    Dipartimento di Scienze Biochimiche A Rossi Fanelli, Sapienza Universita di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy
    Proc Natl Acad Sci U S A 108:20514-9. 2011
    ....
  29. ncbi Mechanisms underlying ubiquitination
    C M Pickart
    School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, Maryland 21205, USA
    Annu Rev Biochem 70:503-33. 2001
    ..The new findings shed light on many aspects of E3 structure, function, and mechanism, but also emphasize that key features of E3 catalysis remain to be elucidated...
  30. pmc MACiE: exploring the diversity of biochemical reactions
    Gemma L Holliday
    EMBL EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
    Nucleic Acids Res 40:D783-9. 2012
    ..We present new tools for exploring the data in MACiE and comparing entries as well as new analyses of the data and new searches, many of which can now be accessed via dedicated Perl scripts...
  31. pmc The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities
    Daneen Schaeffer
    Department of Microbiology and Molecular Genetics, University of Texas Health Science Center Houston, 6431 Fannin Street, MSB 1 212 Houston, Texas 77030, USA
    Nat Struct Mol Biol 16:56-62. 2009
    ..The combination of an endoRNase and an exoRNase activity seems to be a widespread feature of RNA-degrading machines...
  32. ncbi Catalytic versatility and backups in enzyme active sites: the case of serum paraoxonase 1
    Moshe Ben-David
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Mol Biol 418:181-96. 2012
    ..binding the catalytic calcium and activating the hydrolytic water). Overall, the coexistence of multiple conformations and alternative catalytic modes within the same active site underlines PON1's promiscuity and evolutionary potential...
  33. pmc Active site detection by spatial conformity and electrostatic analysis--unravelling a proteolytic function in shrimp alkaline phosphatase
    Sandeep Chakraborty
    Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India
    PLoS ONE 6:e28470. 2011
    ..Finally, we present experimental evidence of the prediction by CLASP by showing that SAP indeed has protease activity in vitro...
  34. ncbi Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit
    Nabil Miled
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Science 317:239-42. 2007
    ..These studies extend our understanding of the architecture of PI3Ks and provide insight into how two classes of mutations that cause a gain in function can lead to cancer...
  35. ncbi Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA
    S D Bruner
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Nature 403:859-66. 2000
    ..One known mutation, R154H, converts hOGG1 to a promutator by relaxing the specificity of the enzyme for the base opposite oxoG...
  36. ncbi Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors
    M S Finnin
    Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 401:188-93. 1999
    ..These structures also suggest a mechanism for the deacetylation reaction and provide a framework for the further development of HDAC inhibitors as antitumour agents...
  37. pmc Structure of human O-GlcNAc transferase and its complex with a peptide substrate
    Michael B Lazarus
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Nature 469:564-7. 2011
    ....
  38. pmc Molecular architecture of the Mos1 paired-end complex: the structural basis of DNA transposition in a eukaryote
    Julia M Richardson
    School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland
    Cell 138:1096-108. 2009
    ..Mixing experiments indicate that a transposase dimer initiates first-strand cleavage and suggest a pathway for PEC formation...
  39. ncbi The conformational plasticity of protein kinases
    Morgan Huse
    Department of Biological Sciences, Stanford University, Palo Alto, California 94305, USA
    Cell 109:275-82. 2002
    ..By contrast, crystal structures of inactive kinases have revealed a remarkable plasticity in the kinase domain that allows the adoption of distinct conformations in response to interactions with specific regulatory domains or proteins...
  40. ncbi Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast
    E Mossessova
    Biochemistry Department, Weill Medical College of Cornell University, New York, New York 10021, USA
    Mol Cell 5:865-76. 2000
    ..Genetic analysis guided by the structure further reveals a regulatory element N-terminal to the proteolytic domain that is required for cell growth in yeast...
  41. ncbi Structure of the protein phosphatase 2A holoenzyme
    Yanhui Xu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Cell 127:1239-51. 2006
    ..This structure reveals significant ramifications for understanding the function and regulation of PP2A...
  42. pmc Origin and evolution of the archaeo-eukaryotic primase superfamily and related palm-domain proteins: structural insights and new members
    Lakshminarayan M Iyer
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health Bethesda, MD 20894, USA
    Nucleic Acids Res 33:3875-96. 2005
    ..These observations point to a functional equivalence of the two classes of primases, which seem to have repeatedly displaced each other in various extrachromosomal replicons...
  43. ncbi Crystal structure of the FTO protein reveals basis for its substrate specificity
    Zhifu Han
    National Institute of Biological Sciences, No 7 Science Park Road, Beijing 102206, China
    Nature 464:1205-9. 2010
    ..Taken together, these results provide a structural basis for understanding FTO substrate-specificity, and serve as a foundation for the rational design of FTO inhibitors...
  44. pmc Structural basis of high-fidelity DNA synthesis by yeast DNA polymerase delta
    Michael K Swan
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York, USA
    Nat Struct Mol Biol 16:979-86. 2009
    ..Taken together, the structure provides a chemical basis for the bulk of DNA synthesis in eukaryotic cells and a framework for understanding the effects of cancer-causing mutations in Pol delta...
  45. pmc Oxidative protein folding by an endoplasmic reticulum-localized peroxiredoxin
    Ester Zito
    Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 40:787-97. 2010
    ..These observations implicate ER-localized PRDX4 in a previously unanticipated, parallel, ERO1-independent pathway that couples hydroperoxide production to oxidative protein folding in mammalian cells...
  46. ncbi WNK1, a novel mammalian serine/threonine protein kinase lacking the catalytic lysine in subdomain II
    B Xu
    Departments of Pharmacology and Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 275:16795-801. 2000
    ..This distinct organization of catalytic residues indicates that WNK1 belongs to a novel family of serine/threonine protein kinases...
  47. pmc An efficient, multiply promiscuous hydrolase in the alkaline phosphatase superfamily
    Bert van Loo
    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom
    Proc Natl Acad Sci U S A 107:2740-5. 2010
    ..PMH is thus one of the most promiscuous hydrolases described to date. The functional links between superfamily activities can be presumed to have played a role in functional evolution by gene duplication...
  48. ncbi The 1.6 A crystal structure of the catalytic domain of PlyB, a bacteriophage lysin active against Bacillus anthracis
    Corrine J Porter
    Protein Crystallography Unit, Department of Biochemistry and Molecular Biology and The ARC Centre of Excellence for Structural and Functional Microbial Genomics, Monash University, Clayton, Melbourne, VIC 3800, Australia
    J Mol Biol 366:540-50. 2007
    ..This molecule comprises an N-terminal catalytic domain (PlyB(cat)) and a C-terminal bacterial SH3-like domain, SH3b...
  49. ncbi Torque generation and elastic power transmission in the rotary F(O)F(1)-ATPase
    Wolfgang Junge
    Department of Biophysics, University of Osnabruck, Barbarastrasse 11, 49076 Osnabruck, Germany
    Nature 459:364-70. 2009
    ..Attempts to understand in detail the mechanisms of torque generation in this simple and robust system have been both aided and complicated by a wealth of sometimes conflicting data...
  50. pmc Medium- and short-chain dehydrogenase/reductase gene and protein families : the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes
    K L Kavanagh
    Structural Genomics Consortium, University of Oxford, United Kingdom
    Cell Mol Life Sci 65:3895-906. 2008
    ..The conserved fold and nucleotide binding emphasize the role of SDRs as scaffolds for an NAD(P)(H) redox sensor system, of importance to control metabolic routes, transcription and signalling...
  51. ncbi Chemistry-based functional proteomics reveals novel members of the deubiquitinating enzyme family
    Anna Borodovsky
    Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Chem Biol 9:1149-59. 2002
    ..We show that this polypeptide reacts with the C terminus of Ub, thus demonstrating DUB-like enzymatic activity for this novel superfamily of proteases...
  52. ncbi Crystal structure of Argonaute and its implications for RISC slicer activity
    Ji Joon Song
    Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Science 305:1434-7. 2004
    ..The architecture of the molecule and the placement of the PAZ and PIWI domains define a groove for substrate binding and suggest a mechanism for siRNA-guided mRNA cleavage...
  53. ncbi Crystal structure of a mammalian voltage-dependent Shaker family K+ channel
    Stephen B Long
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 309:897-903. 2005
    ..Electrostatic properties of the side portals and positions of the T1 domain and beta subunit are consistent with electrophysiological studies of inactivation gating and with the possibility of K+ channel regulation by the beta subunit...
  54. ncbi Structure and mechanism of a bacterial light-regulated cyclic nucleotide phosphodiesterase
    Thomas R M Barends
    Max Planck Institute for Medical Research, Department of Biomolecular Mechanisms, Jahnstrasse 29, 69120 Heidelberg, Germany
    Nature 459:1015-8. 2009
    ..Photon absorption by the BLUF domain of one subunit of the antiparallel BlrP1 homodimer activates the EAL domain of the second subunit through allosteric communication transmitted through conserved domain-domain interfaces...
  55. ncbi Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde
    Min Hu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Cell 111:1041-54. 2002
    ..Binding by ubiquitin aldehyde induces a drastic conformational change in the active site that realigns the catalytic triad residues for catalysis...
  56. ncbi Crystal structure of the maltose transporter in a pretranslocation intermediate state
    Michael L Oldham
    Department of Biological Sciences, Purdue University, Howard Hughes Medical Institute, West Lafayette, IN 47907, USA
    Science 332:1202-5. 2011
    ..These results, interpreted in light of biochemical and functional studies, provide a structural basis to understand allosteric communication in ABC transporters...
  57. pmc Crystal structure of an RluF-RNA complex: a base-pair rearrangement is the key to selectivity of RluF for U2604 of the ribosome
    Akram Alian
    Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158 2517, USA
    J Mol Biol 388:785-800. 2009
    ..The RNA stem-loop is bound to a conserved binding groove in the catalytic domain. A base from a bulge in the stem, A2602, has folded into the stem, forcing one strand of the RNA stem to ..
  58. ncbi Structural basis for natural lactonase and promiscuous phosphotriesterase activities
    Mikael Elias
    Laboratoire de Cristallographie et Modélisation des Matériaux Minéraux et Biologiques, CNRS Université Henri Poincaré, 54506 Nancy, France
    J Mol Biol 379:1017-28. 2008
    ..This example demonstrates that promiscuous activities probably constitute a large and efficient reservoir for the creation of novel catalytic activities...
  59. ncbi Crystal structure of the catalytic alpha subunit of E. coli replicative DNA polymerase III
    Meindert H Lamers
    Howard Hughes Medical Institute, Department of Molecular and Cell Biology and Department of Chemistry, University of California, Berkeley, CA 94720, USA
    Cell 126:881-92. 2006
    ..of a large fragment of Pol III (residues 1-917), reveals a unique chain fold with localized similarity in the catalytic domain to DNA polymerase beta and related nucleotidyltransferases...
  60. ncbi The structure of T. aquaticus DNA polymerase III is distinct from eukaryotic replicative DNA polymerases
    Scott Bailey
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Cell 126:893-904. 2006
    The crystal structure of Thermus aquaticus DNA polymerase III alpha subunit reveals that the structure of the catalytic domain of the eubacterial replicative polymerase is unrelated to that of the eukaryotic replicative polymerase but ..
  61. ncbi Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase
    Kenji Kamata
    Banyu Tsukuba Research Institute in collaboration with Merck Research Laboratories, Okubo 3, Tsukuba, Ibaraki 300 2611, Japan
    Structure 12:429-38. 2004
    ..This finding provided the mechanistic basis for activation of glucokinase as a potential therapeutic approach for treating type 2 diabetes mellitus...
  62. pmc Specificity prediction of adenylation domains in nonribosomal peptide synthetases (NRPS) using transductive support vector machines (TSVMs)
    Christian Rausch
    Center for Bioinformatics Tübingen ZBIT, University of Tubingen, Germany
    Nucleic Acids Res 33:5799-808. 2005
    ..None of the predictive methods could infer any specificity for 2.4% of the sequences, suggesting completely new types of specificity...
  63. pmc Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation
    Peter Rellos
    University of Oxford, Nuffield Department of Clinical Medicine, Structural Genomics Consortium, Oxford, United Kingdom
    PLoS Biol 8:e1000426. 2010
    ..complex, the inhibitory region adopted an extended conformation and interacted with an adjacent catalytic domain positioning T287 into the active site of the interacting protomer...
  64. pmc Networks of high mutual information define the structural proximity of catalytic sites: implications for catalytic residue identification
    Cristina Marino Buslje
    Fundacion Instituto Leloir, Buenos Aires, Argentina
    PLoS Comput Biol 6:e1000978. 2010
    ....
  65. pmc A measure of the promiscuity of proteins and characteristics of residues in the vicinity of the catalytic site that regulate promiscuity
    Sandeep Chakraborty
    Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India
    PLoS ONE 7:e32011. 2012
    ..05). Since it is known that these characteristics are key factors in catalysis, their relationship with the promiscuity index cross validates the methodology of PROMISE...
  66. ncbi The oligomeric conformation of peroxiredoxins links redox state to function
    Sergio Barranco-Medina
    Biochemistry and Physiology of Plants, Bielefeld University, Bielefeld, Germany
    FEBS Lett 583:1809-16. 2009
    ....
  67. pmc The intrinsic dynamics of enzymes plays a dominant role in determining the structural changes induced upon inhibitor binding
    Ahmet Bakan
    Department of Computational Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Proc Natl Acad Sci U S A 106:14349-54. 2009
    ..The results suggest that simple but robust rules encoded in the protein structure play a dominant role in predefining the mechanisms of ligand binding, which may be advantageously exploited in designing inhibitors...
  68. pmc Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases
    Beth Apsel
    Program in Chemistry and Chemical Biology, University of California, San Francisco, 600 16th Street, San Francisco, California 94158, USA
    Nat Chem Biol 4:691-9. 2008
    ..These molecules demonstrate the feasibility of accessing a chemical space that intersects two families of oncogenes...
  69. pmc Unconventional serine proteases: variations on the catalytic Ser/His/Asp triad configuration
    Ozlem Dogan Ekici
    Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, USA
    Protein Sci 17:2023-37. 2008
    ..This work discusses the structure and function of these novel serine proteases and threonine proteases and how their catalytic machinery differs from the prototypic serine protease class...
  70. pmc A dynamic knockout reveals that conformational fluctuations influence the chemical step of enzyme catalysis
    Gira Bhabha
    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 332:234-8. 2011
    ....
  71. pmc The mechanism for activation of GTP hydrolysis on the ribosome
    Rebecca M Voorhees
    MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
    Science 330:835-8. 2010
    ..The structure suggests a universal mechanism for GTPase activation and hydrolysis in translational GTPases on the ribosome...
  72. pmc Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance
    Stephen Hare
    Division of Infectious Diseases, Imperial College London, London W2 1PG, United Kingdom
    Proc Natl Acad Sci U S A 107:20057-62. 2010
    ..Furthermore, our structures predict physical proximity and an interaction between HIV-1 IN mutant residues His148 and Ser/Ala140, rationalizing the coevolution of Q148H and G140S/A mutations in drug-resistant viral strains...
  73. ncbi ATP synthase--a marvellous rotary engine of the cell
    M Yoshida
    Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta 4259, Yokohama 226 8503, Japan
    Nat Rev Mol Cell Biol 2:669-77. 2001
    ..The mechanisms by which rotation and catalysis are coupled in the working enzyme are now being unravelled on a molecular scale...
  74. pmc Functional and structural characterization of the integrase from the prototype foamy virus
    Eugene Valkov
    Division of Medicine, St Mary s Campus, Imperial College London, London, UK
    Nucleic Acids Res 37:243-55. 2009
    ....
  75. ncbi Structural basis of RNA polymerase II backtracking, arrest and reactivation
    Alan C M Cheung
    Department of Biochemistry, Ludwig Maximilians Universitat Munchen, Feodor Lynen Str 25, 81377 Munich, Germany
    Nature 471:249-53. 2011
    ..These results establish the structural basis of Pol II backtracking, arrest and reactivation, and provide a framework for analysing gene regulation during transcription elongation...
  76. pmc ATR-dependent phosphorylation of DNA-dependent protein kinase catalytic subunit in response to UV-induced replication stress
    Hirohiko Yajima
    Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, 2201 Inwood Rd, NC7 502, Dallas, TX 75390 9187, USA
    Mol Cell Biol 26:7520-8. 2006
    ..Taken together, these results strongly suggest that DNA-PKcs is required for the cellular response to replication stress and might play an important role in the repair of stalled replication forks...
  77. pmc An artificial di-iron oxo-protein with phenol oxidase activity
    Marina Faiella
    Department of Chemistry, University Federico II of Napoli, Complesso Universitario Monte S Angelo, Italy
    Nat Chem Biol 5:882-4. 2009
    ..Sufficient stability was, however, obtained by optimizing the sequence of a loop distant from the active site...
  78. pmc Ligand binding and substrate discrimination by UDP-galactopyranose mutase
    Todd D Gruber
    Department of Biochemistry, University of Wisconsin Madison, Madison, WI 53706 1544, USA
    J Mol Biol 391:327-40. 2009
    ..To understand the consequences of these differences, we derived a model for the productive UGM-substrate complex that highlights interactions that can contribute to catalysis and substrate discrimination...
  79. ncbi Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor
    Y Chen
    Department of Pharmacology, Joan and Sanford I Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Science 289:625-8. 2000
    ..sAC is also expressed in other bicarbonate-responsive tissues, which suggests that bicarbonate regulation of cAMP signaling plays a fundamental role in many biological systems...
  80. ncbi Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase
    Jinrong Min
    W M Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Cell 112:711-23. 2003
    ..We have solved a 2.5 A resolution structure of the catalytic domain of human Dot1, hDOT1L, in complex with S-adenosyl-L-methionine (SAM)...
  81. pmc Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation
    Da Jia
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Nature 449:248-51. 2007
    ..we show, with the use of crystallography, that the carboxy-terminal domain of human Dnmt3L interacts with the catalytic domain of Dnmt3a, demonstrating that Dnmt3L has dual functions of binding the unmethylated histone tail and ..
  82. ncbi Accurate sequence-based prediction of catalytic residues
    Tuo Zhang
    College of Mathematical Science and LPMC, Nankai University, Tianjin, PRC
    Bioinformatics 24:2329-38. 2008
    ..We propose a sequence-based catalytic residue predictor that provides predictions with quality comparable to modern structure-based methods and that exceeds quality of state-of-the-art sequence-based methods...
  83. pmc Active site prediction using evolutionary and structural information
    Sriram Sankararaman
    Computer Science Division, University of California, Berkeley, USA
    Bioinformatics 26:617-24. 2010
    ....
  84. ncbi Structure of Escherichia coli RNase E catalytic domain and implications for RNA turnover
    Anastasia J Callaghan
    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK
    Nature 437:1187-91. 2005
    ..Here we report crystal structures of the catalytic domain of RNase E as trapped allosteric intermediates with RNA substrates...
  85. ncbi The 2009 pandemic H1N1 neuraminidase N1 lacks the 150-cavity in its active site
    Qing Li
    CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
    Nat Struct Mol Biol 17:1266-8. 2010
    ..In contrast to other characterized N1 neuraminidases, which are all members of group 1, 2009 H1N1 neuraminidase does not have a 150-cavity...
  86. pmc The TFIIF-like Rpc37/53 dimer lies at the center of a protein network to connect TFIIIC, Bdp1, and the RNA polymerase III active center
    Chih Chien Wu
    Department of Life Sciences and Institute of Genome Sciences, National Yang Ming University, Taipei, Taiwan, Republic of China
    Mol Cell Biol 31:2715-28. 2011
    ..Our work explains how the Rpc37/53 dimer is anchored on the Pol III core and acts as a hub to integrate a protein network for initiation and termination...
  87. pmc Catalytic mechanism of RNA backbone cleavage by ribonuclease H from quantum mechanics/molecular mechanics simulations
    Edina Rosta
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Am Chem Soc 133:8934-41. 2011
    ..Proton-transfer reactions and changes in the metal ion coordination emerge as central factors in the RNA-cleavage reaction...
  88. ncbi Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA
    Robert P Gibson
    Department of Chemistry, The University of York, York YO10 5YW, Heslington, United Kingdom
    Chem Biol 9:1337-46. 2002
    ..The overall structure and the intimate details of the catalytic machinery reveal a striking similarity to glycogen phosphorylase, indicating a strong evolutionary link and suggesting a common catalytic mechanism...
  89. pmc Dissection of Pol II trigger loop function and Pol II activity-dependent control of start site selection in vivo
    Craig D Kaplan
    Department of Biochemistry and Biophysics, Texas A and M University, College Station, Texas, United States of America
    PLoS Genet 8:e1002627. 2012
    ..Finally, we connect Pol II activity to transcription start site selection in vivo, implicating the Pol II active site and transcription itself as a driver for start site scanning, contravening current models for this process...
  90. ncbi Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling
    Marco Conti
    Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 943095 5317, USA
    Annu Rev Biochem 76:481-511. 2007
    ....
  91. ncbi Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
    Paul T C Wan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Cell 116:855-67. 2004
    ..The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism...
  92. ncbi Structure-stability-activity relationship in covalently cross-linked N-carbamoyl D-amino acid amidohydrolase and N-acylamino acid racemase
    Wei Chun Chiu
    Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, 30013, ROC
    J Mol Biol 359:741-53. 2006
    ..2-fold at 65 degrees C). Furthermore, molecular dynamic simulations reveal that A302C substantially sustains the fine-tuned catalytic site as temperature increases, achieving enhanced activity...
  93. ncbi Protein kinase M zeta synthesis from a brain mRNA encoding an independent protein kinase C zeta catalytic domain. Implications for the molecular mechanism of memory
    A Ivan Hernandez
    Department of Physiology, State University of New York Downstate Medical Center, Brooklyn, 11203, USA
    J Biol Chem 278:40305-16. 2003
    ..PKM zeta is the independent catalytic domain of the atypical PKC zeta isoform and produces long term effects at synapses because it is persistently active,..
  94. pmc The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation
    Sotiria Palioura
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Science 325:321-5. 2009
    ..The tRNA binding is likely to induce a conformational change in the enzyme's active site that allows a phosphoserine covalently attached to tRNA(Sec), but not free phosphoserine, to be oriented properly for the reaction to occur...
  95. pmc A cytidine deaminase edits C to U in transfer RNAs in Archaea
    Lennart Randau
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Science 324:657-9. 2009
    ..The presence of this C-to-U editing enzyme guarantees the proper folding and functionality of all M. kandleri tRNAs...
  96. pmc RNA polymerase II with open and closed trigger loops: active site dynamics and nucleic acid translocation
    Michael Feig
    Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, USA
    Biophys J 99:2577-86. 2010
    ....
  97. ncbi Improved solubility of TEV protease by directed evolution
    Susanne van den Berg
    Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE 171 77 Stockholm, Sweden
    J Biotechnol 121:291-8. 2006
    ..We identified a mutant, TEV(SH), in which three amino acid substitutions result in a five-fold increase in the yield of purified protease with retained activity...
  98. pmc Structural basis for the suppression of skin cancers by DNA polymerase eta
    Timothy D Silverstein
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, New York 10029, USA
    Nature 465:1039-43. 2010
    ....
  99. pmc Central role of the RNA polymerase trigger loop in intrinsic RNA hydrolysis
    Yulia Yuzenkova
    Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, United Kingdom
    Proc Natl Acad Sci U S A 107:10878-83. 2010
    ..We obtained similar results with Escherichia coli RNA polymerase, indicating that the function of the TL in phosphodiester bond hydrolysis is conserved among bacteria...
  100. pmc On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm
    Enrique Marcos
    Department of Biological Chemistry and Molecular Modelling, IQAC CSIC, Barcelona, Spain
    PLoS Comput Biol 6:e1000738. 2010
    ....
  101. pmc Unique biological properties of catalytic domain directed human anti-CAIX antibodies discovered through phage-display technology
    Chen Xu
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 5:e9625. 2010
    ..These human anti-CAIX antibodies are important reagents for development of new immunotherapies and diagnostic tools for RCC treatment as well as extending our knowledge on the basic structure-function relationships of the CAIX molecule...

Research Grants71

  1. Inhibition of IkK to treat lethal Graft-vs.-Host Disease
    Patrick Flood; Fiscal Year: 2009
    ..This drug is an inhibitor of the catalytic domain of IKK ? and blocks the activation of NF-?B by interfering with the phosphorylation of I?B...
  2. Cyclic AMP Signaling in Pseudomonas aeruginosa Virulence
    Matthew C Wolfgang; Fiscal Year: 2011
    ..CyaB is a member of the inorganic carbon-activated family of adenylate cyclases and the CyaB catalytic domain is stimulated by HCO3- in vitro and by increased extracellular CO2 when expressed in P. aeruginosa...
  3. PHOSPHOPEPTIDE METABOLISM IN ADIPOCYTES
    Joseph Avruch; Fiscal Year: 2013
    ..We hypothesize a two step process;first, Rheb-GTP interacts with the mTOR catalytic domain and with FKBP38, an endogenous inhibitor of mTOR, to convert the mTOR catalytic domain into an active form...
  4. Activation of PI Specific Phospholipase C Enzymes
    MARY FEDARKO ROBERTS; Fiscal Year: 2013
    ..The bacterial PI-PLC enzymes, single domain proteins structurally equivalent to the catalytic domain of the mammalian enzymes, are usually secreted and often aid in the infection of target cells...
  5. Hunting for Endogenous Ligands for Invariant Natural Killer T Cells
    Peng George Wang; Fiscal Year: 2010
    ..iGb3S identified in any human tissue by analysis of the iGb3S mRNA, and the chimeric molecules containing the catalytic domain of human iGb3S did not show any functional activity in synthesis of iGb3 due to at least one amino acid ..
  6. The Role of DNMT3B in the DNA Methylation of Cancer Cells
    LUCY ANN GODLEY; Fiscal Year: 2012
    ..produces DNMT3B transcripts containing premature stop codons and encoding truncated proteins lacking the catalytic domain. Tissue culture cells expressing DNMT3B7, the most frequently observed aberrant DNMT3B transcript in cancer ..
  7. Mechanism and role of DLC-1 tumor suppressor loss in lung cancer
    Channing J Der; Fiscal Year: 2012
    ..However, in addition to a RhoGAP catalytic domain, DLC-1 also contains START lipid-binding and SAM protein-protein interaction domains...
  8. Role of chromatin structure in regulating gene silencing
    Mary Bryk; Fiscal Year: 2009
    ..assays for COMPASS function will advance the molecular characterization of this evolutionarily conserved catalytic domain. Second, the histone composition of rDNA chromatin will be analyzed using molecular and genetic approaches...
  9. Interactions between Bacterial Tyrosine Kinases and Phosphatases
    Ranajeet Ghose; Fiscal Year: 2013
    ..module for BY-kinases is a cluster of tyrosine residues (YC) in the C-terminal tail of its cytosolic catalytic domain. The YC is autophosphorylated in an intermolecular fashion and dephosphorylated by low molecular weight ..
  10. Molecular Mechanisms of Histone Acetyltransferases
    John M Denu; Fiscal Year: 2012
    ..b>catalytic domain selectivity and b.) modular histone-binding domains that recognize distinct patterns of PTMs...
  11. Bordetella adenylate cyclase toxin: the role of cell interaction in toxin functio
    JOSHUA CLARK EBY; Fiscal Year: 2013
    ..AC toxin intoxicates host cells by binding to the cell membrane and translocating its catalytic domain across the lipid-bilayer, resulting in unregulated generation of intracellular cAMP...
  12. Identifying and testing new targets for Parkinson Disease gene therapy
    Nicholas Muzyczka; Fiscal Year: 2013
    ..1) To use PLD2 mutants to determine which of the PLD2 functional domains is responsible for PLD2 toxcity, its catalytic domain or its protein interaction domains, 2) To identify the kinase that phosphorylates ? syn in vivo, 3) To test ..
  13. Re-expression of Aberrantly Silenced Genes Induced by Polyamine Analogues
    Robert A Casero; Fiscal Year: 2013
    ..The catalytic domain of LSD1 is homologous to the FAD-dependent spermine oxidase (SMO)...
  14. A new tool for the cell-specific identification of RNA binding protein targets
    Michael Rosbash; Fiscal Year: 2013
    ..It involves creating a fusion protein between an RBP and the catalytic domain of a RNA editing enzyme like ADAR (adenosine deaminase)...
  15. PCSK9, Lipoprotein receptors, and Atherosclerosis
    Sergio Fazio; Fiscal Year: 2013
    ..The catalytic domain (CA, residues 153-449), which contains a proteolytic site masked and neutralized by the associated PD;3...
  16. DAPK1 regulation of NMDA receptors in ischemic neuronal death
    NICOLAS GUILLERMO BAZAN; Fiscal Year: 2012
    ..Subsequently, we have generated genetically modified mice (cdDAPK1), in which catalytic domain of DAPK1 is selectively deleted...
  17. DNA Methylation: Structures, Functions, and Regulation
    Xiaodong Cheng; Fiscal Year: 2013
    ..Mammalian DNA methyltransferases, Dnmt1 and Dnmt3a, each contain a C-terminal catalytic domain and a largely uncharacterized N-terminal region including several distinct regulatory domains...
  18. Regulation and Neural Function of Atypical PKC
    Todd C Sacktor; Fiscal Year: 2011
    ..Unlike other PKC isoforms that require second messengers for activation, PKM6 consists of an independent PKC catalytic domain that is constitutively active...
  19. Dual Function of VPO1 in Pathogen Recognition and Killing
    Guangjie Cheng; Fiscal Year: 2013
    ..VPO1 is unique among the members of hPx family in that it contains a catalytic domain at its C-terminus and a large N-terminal region including five leucine-rich regions (LRRs) and four ..
  20. Structural and functional effects of oxidative modification of myosin
    REBECCA J MOEN; Fiscal Year: 2013
    ..in myosin are responsible for these effects, which result from specific structural perturbations in the catalytic domain of myosin...
  21. Novel Mechanisms of C-Kit Regulation in Mast Cells
    Reuben Kapur; Fiscal Year: 2013
    ..KIT alone has been ineffective;particularly in patients that harbor the activating mutation of KIT in the catalytic domain, KITD816V, which are completely resistant to imatinib or second generation tyrosine kinase inhibitors...
  22. Precision engineering of DNA methylation patterns in the human genome
    Ryan Lister; Fiscal Year: 2013
    ..highly specific TALE-DBDs able to recognize unique ~20 bp sequences in the genome, and linked to either the catalytic domain of DNA methyltransferase 3a (DNMT3A) for de novo DNAme, or VP64 or the TET1 for targeted DNA demethylation...
  23. Structural basis of mRNA decapping by Dcp2: conformational changes &co-activator
    JEFFREY SCOTT MUGRIDGE; Fiscal Year: 2013
    ..role played by coactivators of decapping, NMR spectroscopy will be used to identify contacts between the catalytic domain of Dcp2 and coactivators Dcp1 and Edc1 that might be protein-protein interaction surfaces that promote the ..
  24. AN HTS ASSAY FOR INHIBITORS OF C. DIFFICLE TOXINS
    David B Haslam; Fiscal Year: 2013
    ..We have cloned and expressed the catalytic domain of TcdB, developed two assays to detect its activity, and have adapted both assays to 384-well format...
  25. Structure and Cell-Wall Targeting of the Staphylolytic Enzyme Lysostaphin
    KEITH GRISCOM INMAN; Fiscal Year: 2010
    ..C-terminal cell-wall targeting domain binds the catalytic substrate and is required for full activity of the catalytic domain, but the precise requirements for targeting are not known...
  26. Differential regulation of Ras nucleotide exchange factors
    JEFFREY SCOTT IWIG; Fiscal Year: 2012
    ..be elucidated by measuring nucleotide exchange activity of different RasGrp1 constructs that contain only the catalytic domain or this domain with the C-terminal EF-hands, C1 domain and coiled-coil motif...
  27. Structure and mechanism of CpG specific DNA glycosylases
    ALEX C DROHAT; Fiscal Year: 2013
    ..ii) We will determine the crystal structure of TDG (catalytic domain) bound to DNA containing a non-cleavable substrate analog, revealing interactions that promote G...
  28. The Biology and Biochemistry of ADAR RNA Editing Enzymes
    Brenda L Bass; Fiscal Year: 2013
    ..Experiments are proposed to determine the amino acids in the human ADAR2 catalytic domain that control its catalytic efficiency and lead to targeting of precise adenosines...
  29. Genetic and epigenetic contributions to the neonatal Th2 bias
    REBECCA D ADKINS; Fiscal Year: 2013
    ..Constructs containing a CNS-1-targeted zinc finger protein coupled to the catalytic domain of the de novo DNA methyltransferase Dnmt3a will be created~ expression of the constructs will be confined to ..
  30. Analysis of the immunological role of Phospholipase D4
    David Nemazee; Fiscal Year: 2013
    ..Pld4 carries a conserved phospholipase D catalytic domain with active site histidine, lysine and aspartic acid (HKD motif), but otherwise differs significantly frm ..
  31. PARP activity in allergic inflammation
    Mark H Kaplan; Fiscal Year: 2012
    ..Owing to the presence of macro domains and the PARP (poly ADP-ribose polymerase) catalytic domain, CoaSt6 belongs to the PARP family of proteins and is also called PARP-14...
  32. Small Molecule Inhibitors of ZAP-70 for the Treatment of Autoimmune Disorders
    Mark Gallop; Fiscal Year: 2013
    ..ZAP-70 catalytic site inhibitors, without success, likely due to specific structural attributes of the kinase catalytic domain. Following TCR stimulation, the ZAP-70 tandem SH2 domains associate with dual tyrosine phosphorylated ..
  33. Mechanisms of Oxygen Sensing
    ROBERT BRIAN HAMANAKA; Fiscal Year: 2010
    ..We will thus further explore the role of mitochondrial ROS in regulating the cellular hypoxic response. ..
  34. Structure and mechanism of the AMP-activated protein kinase
    Lawrence Shapiro; Fiscal Year: 2010
    ..This complex lacks the kinase catalytic domain, but reveals the conserved trimeric core architecture of AMPKs...
  35. Regulation and Neural Function of Atypical PKC
    Todd C Sacktor; Fiscal Year: 2013
    ..Unlike other PKC isoforms that require second messengers for activation, PKM6 consists of an independent PKC catalytic domain that is constitutively active...
  36. PROTEIN KINASE C ISOZYMES IN HIPPOCAMPAL PLASTICITY
    Todd C Sacktor; Fiscal Year: 2013
    ..Produced from a PKM6 mRNA, PKM6 is the independent catalytic domain of PKC6, which, lacking an autoinhibitory regulatory domain, persistently phosphorylates without second ..
  37. Function of NS2 in Hepatitis C Virus Assembly and Release
    Minkyung Yi; Fiscal Year: 2012
    ..Our hypothesis that "NS2 protein, which was known to contain a catalytic domain of NS2/NS3 protease, plays a critical role in HCV assembly and release" is derived from our extensive ..
  38. METALLOPROTEINASES IN TUMOR NEOVASCULARIZATION
    Alex Y Strongin; Fiscal Year: 2013
    ..The several individual structural domains which are distinct from and additional to the catalytic domain play a well-controlled role in the interactions of MT1-MMP with its targets and also in the multiple ..
  39. MOLECULAR DYNAMICS OF MUSCLE CONTRACTION
    David D Thomas; Fiscal Year: 2013
    ..2) Structural dynamics of the myosin catalytic domain will be probed to test and revise mechanistic models...
  40. Pathophysiological Redox Regulation of JAK2 in Diabetes
    ROY DUHE; Fiscal Year: 2009
    ..Sustained oxidative stress impairs JAK2's kinase activity by oxidizing a "redox switch" in its catalytic domain, and the resulting loss of signal throughput causes pathological consequences in a cell-dependent fashion...
  41. Cytomegalovirus Deubiquitinase pUL48: Identifying Substrate and Inhibitors
    D WADE GIBSON; Fiscal Year: 2010
    ..Its catalytic domain lies within a 300 to 400 amino-acid sequence that is the amino terminal end of the largest protein encoded by ..
  42. Mechanistic Analysis Of Microtubule Based Motors
    Susan P Gilbert; Fiscal Year: 2013
    ..Kinesin superfamily members share a common catalytic domain yet participate in a wide range of cellular functions including intracellular transport, mitosis and meiosis, ..
  43. Magnetic Resonance Probes of Structural Changes in Aging Muscle
    RYAN N MELLO; Fiscal Year: 2012
    ..goal of this research is to determine the effect of aging on force-dependent structural changes in the catalytic domain (CD) and light chain domain (LCD) of the myosin head in rat muscle fibers...
  44. Structure and Function of Carboxypeptidases
    Randal A Skidgel; Fiscal Year: 2013
    ..the B1R is mediated by its C-terminal domain whereas allosteric modulation is mediated by a surface near the catalytic domain. We will: (i) determine whether CPM and B1R directly interact...
  45. Fibroblast Activation Protein in the Tumor Microenvironment in Lung Cancer
    ELLEN PURE apos PURE'; Fiscal Year: 2013
    ..FAP contains a structurally defined catalytic domain that mediates its protease activities...
  46. Elucidating the Molecular Mechanisms of Ect2 in cytokinesis and oncogenesis
    DANIELLE RYAN COOK; Fiscal Year: 2012
    ..This mislocalization may lead to inappropriate Rho activation in the cytoplasm. In addition to its RhoGEF catalytic domain, Ect2 is comprised of multiple addition domains...
  47. Regulation of Neutral Sphingomyelinase 2 by Inter-Domain Interactions
    MICHAEL VIRGIL AIROLA; Fiscal Year: 2012
    ..We will determine binding affinities of N-terminal peptides to the catalytic domain and determine crystal structures of the catalytic domain alone and bound to N-terminal peptides...
  48. Mechanism of allosteric signal integration in Src tyrosine kinase
    ZACHARIAH HUSSEIN FODA; Fiscal Year: 2013
    ..of the kinase and may thus facilitate integration of allosteric signals into the regulation of protein kinase catalytic domain activity...
  49. Histone Modification Mechanisms and Inhibition
    Philip A Cole; Fiscal Year: 2012
    ..we plan to build on our recent progress regarding structural analysis of the p300/CBP HAT domain and the LSD1 catalytic domain in complex with our synthetic inhibitors...
  50. Mechanisms of Long-Term Memory Maintenance in Aplysia.
    David L Glanzman; Fiscal Year: 2013
    ..PKM[unreadable] contains the catalytic domain of an atypical PKC, but lacks the regulatory domain and is therefore constitutively active...
  51. Regulation of soluble guanylyl cyclase, the NO-receptor
    Annie V Beuve; Fiscal Year: 2013
    ..signaling enzyme that contains the NO receptor-heme domain, a dimerization domain and the effector-catalytic domain. It is not known how the NO signal is propagated to the catalytic domain of sGC...
  52. Structure and mechanism of signal peptide peptidase
    Michael S Wolfe; Fiscal Year: 2010
    ..that the C- terminal half of SPP alone is catalytically active;we seek to biochemically characterize this catalytic domain and work toward its structure by NMR...
  53. Catalytic Domain Dynamics in Protein Kinases
    Ranajeet Ghose; Fiscal Year: 2013
    ..Even with the availability of multiple crystal structures of active and inactive forms of the SFK catalytic domain, a complete understanding of its catalytic regulation is unavailable...
  54. Structural basis of specificity in affinity-labeled polyketide synthase didomains
    Janet L Smith; Fiscal Year: 2012
    ..requires an understanding of the basis for substrate specificity and stereochemical outcome for each catalytic domain, which at present is lacking...
  55. NON-PROTEOLYTIC INTERACTIONS OF TIMP-2 AND MT1-MMP
    Paolo Mignatti; Fiscal Year: 2013
    ..activity of MT1-MMP is required for tumor cell invasion and proliferation, and that TIMP-2 binds to the catalytic domain of MT1-MMP and blocks its proteolytic activity...
  56. The Structural Basis for Control of 5-Lipoxgenease Activity
    Marcia E Newcomer; Fiscal Year: 2013
    ..We propose experiments to define the interaction of 5-LOX with the bilayer and determine whether the catalytic domain interacts with the membrane as well, and whether FLAP hands off the substrate to the enzyme, or simply ..
  57. Conformational Flexibility in Activation of Scr-Kinase
    Benoit Roux; Fiscal Year: 2013
    ..All nine members of the Src family are large allosteric multi-domain enzymes formed by a catalytic domain which is preceded by two peptide binding modules, the Src-homology domains SH2 and SF13...
  58. Structure-Function Relationships in Kinetoplastid RNA-Editing
    WILHELMUS HOL; Fiscal Year: 2009
    ..builds on recent successes including the crystal structure determinations of the RNA Editing Ligase 1 catalytic domain and that of the editing 3'-Terminal-Uridylylate Transferase...
  59. Proof-of-Principle Studies of DAS181 for Parainfluenza Virus Infection
    Fang Fang; Fiscal Year: 2010
    ..DAS181 is a recombinant fusion protein composed of a sialidase catalytic domain fused with an epithelium-anchoring sequence which functions by eliminating sialic acids on the airway ..
  60. Mechanism and Function of Protein Ubiquitination
    Jon Huibregtse; Fiscal Year: 2013
    ..novel approach for HECT E3 substrate identification, based on the unique mechanism and structure of the catalytic domain. Aim 3 represents a new research direction, where we have applied approaches developed in our ISG15 studies ..
  61. Cooperation of Mutant TP53 and PIK3CA in Breast Carcinogensis
    SARAH E CROESSMANN; Fiscal Year: 2013
    ..In 2004, the Park lab identified PIK3CA, the gene encoding the catalytic domain of PI3K alpha, as the most mutated oncogene in human breast cancer...
  62. Mechanisms of Membrane Translocation by Protein Toxins
    Suren A Tatulian; Fiscal Year: 2013
    ..First, the uniformly 13C-labeled catalytic domain of DT will be expressed in E. coli and disulfide bridged to the unlabeled B-chain or the T-domain...
  63. REGULATION OF IMMUNE RESPONSE IN THE ORAL CAVITY
    Suzanne Michalek; Fiscal Year: 2003
    ..mutans antigens to be used are the saliva-binding region (SBR) of the adhesin AgI/II and the catalytic domain (CAT) and glucan-binding domain (GLU) of glucosyltransferase...
  64. Identification of Drug Targets for NF1
    Yolanda Sanchez; Fiscal Year: 2010
    ..Expression of the catalytic domain of human NF1 can suppress the phenotypes of ira yeast mutants...
  65. MOLECULAR BIOLOGY OF BRAIN PROTEIN PHOSPHORYLATION
    James Sikela; Fiscal Year: 1993
    ..will be screened with two sets of degenerate oligonucleotide probes derived from conserved regions of the catalytic domain of known protein-serine kinase...
  66. TYPE V COLLAGENASE IN RHEUMATOID ARTHRITIS
    Tayebeh Pourmotabbed; Fiscal Year: 2001
    ..Substantiate the hypothesis that a salt linkage present in gelatinase B catalytic domain is responsible for Ca2+-independent activity of the enzyme...
  67. STRUCTURAL UNDERSTANDING OF PHENYLKETONURIA (PKU)
    RAYMOND STEVENS; Fiscal Year: 2004
    ..The structures of the catalytic domain of human phenylalanine hydroxylase, catalytic domain plus tetramerization domain, catalytic domain plus ..
  68. Structural Biology of the Catalytic Domain of Bacteriophage T4 Primase
    David Rovnyak; Fiscal Year: 2009
    ..The proposed work will reveal new structural information on T4 primase and will lay out a pathway for structural studies of larger parts of the T4 replication system. ..
  69. Ribonuclease III mechanism of double-strand RNA cleavage
    ALLEN NICHOLSON; Fiscal Year: 2003
    ..The specific aims of the project are to: (1) determine the functional roles of conserved amino acids in the catalytic domain. To accomplish this, RNase Ill mutants with substitutions of conserved catalytic domain residues will be ..
  70. Treatment of Anthrax with Nonantimicrobial Tetracyclines
    Sanford Simon; Fiscal Year: 2003
    ..Lethal Factor (LeF), the proteolytic subunit of LeTx, is a zinc metalloprotease with a catalytic domain similar to thermolysin and is a potential target of the CMTs as well...
  71. MAMMALIAN SPERM SURFACE MANNOSIDASE
    DAULAT TULSIANI; Fiscal Year: 2003
    ..The enzyme is an intrinsic plasma membrane (PM) protein with its catalytic domain oriented towards the outer surface of the intact spermatozoa...