E Di Cera

Summary

Affiliation: Washington University School of Medicine
Country: USA

Publications

  1. ncbi request reprint Thrombin: a paradigm for enzymes allosterically activated by monovalent cations
    Enrico Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    C R Biol 327:1065-76. 2004
  2. ncbi request reprint A structural perspective on enzymes activated by monovalent cations
    Enrico Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 281:1305-8. 2006
  3. ncbi request reprint Thrombin allostery
    Enrico Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    Phys Chem Chem Phys 9:1291-306. 2007
  4. pmc Serine proteases
    Enrico Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110, USA
    IUBMB Life 61:510-5. 2009
  5. ncbi request reprint Thrombin as procoagulant and anticoagulant
    E Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University Medical School, St Louis, MO 63110, USA
    J Thromb Haemost 5:196-202. 2007
  6. pmc Thrombin
    Enrico Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University Medical School, St Louis, MO 63110, United States
    Mol Aspects Med 29:203-54. 2008
  7. pmc Theory of allosteric effects in serine proteases
    E Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Biophys J 70:174-81. 1996
  8. ncbi request reprint Determinants of specificity in coagulation proteases
    M J Page
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Thromb Haemost 3:2401-8. 2005
  9. ncbi request reprint Molecular mechanisms of thrombin function
    E Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell Mol Life Sci 53:701-30. 1997
  10. pmc Na+ binding to meizothrombin desF1
    M E Papaconstantinou
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell Mol Life Sci 65:3688-97. 2008

Collaborators

  • Swati Prasad
  • Gabriel Waksman
  • J W Weisel
  • Z Chen
  • K P Hopfner
  • Nikos E Tsopanoglou
  • Kevin R Siebenlist
  • Bruce E Maryanoff
  • Stefano Gianni
  • Michael W Mosesson
  • Michael N Greco
  • Andras Gruber
  • Alireza R Rezaie
  • Lisa K Minor
  • ELLEN LEMOSY
  • John R Shainoff
  • Agustin O Pineda
  • F Scott Mathews
  • Michael J Page
  • Prafull S Gandhi
  • Alaji Bah
  • Leslie A Bush
  • Francesca Marino
  • Leslie A Bush-Pelc
  • Christopher J Carrell
  • Thierry Rose
  • Maxwell M Krem
  • M E Papaconstantinou
  • M J Page
  • Angelene M Cantwell
  • Y M Ayala
  • Kevin M Bobofchak
  • Sonia Caccia
  • Savvas N Savvides
  • Weiling Niu
  • A Bah
  • Michelle A Berny
  • Laura C Garvey
  • Clemens Feistritzer
  • T Rose
  • Kristen E Mengwasser
  • Hong Xu
  • Lawrence de Garavilla
  • Matthew E Papaconstantinou
  • Likui Yang
  • D B Roy
  • D Arosio
  • M M Krem
  • Austin Vogt
  • Leslie A Pelc
  • Leslie Bush-Pelc
  • Owen J T McCarty
  • Tara C White
  • P S Gandhi
  • Erik I Tucker
  • E R Guinto
  • Can E Ergenekan
  • Jingping Ge
  • Reto A Schuepbach
  • Ryan W Nelson
  • Steve Wong
  • Laurent O Mosnier
  • E Di Stasio
  • Ross T A MacGillivray
  • Matthias Riewald
  • John H Griffin
  • Mark R Bleackley
  • Narayanasami Sukumar
  • Claudia K Derian
  • Bruce P Damiano
  • Peter Shih
  • Thomas W Corcoran
  • Edward C Giardino
  • Barbara J Haertlein
  • Patricia Andrade-Gordon
  • Christodoulos S Flordellis
  • Jack A Kauffman
  • Michael E Maragoudakis
  • Annette J Eckardt
  • Grace I Wells
  • R T A Macgillivray
  • Enriqueta R Guinto
  • E G Véscovi
  • Erli Zhang
  • Alexander Tulinsky
  • Dolly Banerjee-Roy
  • James B Skeath
  • A M Cantwell
  • L A Bush
  • K Futterer

Detail Information

Publications69

  1. ncbi request reprint Thrombin: a paradigm for enzymes allosterically activated by monovalent cations
    Enrico Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    C R Biol 327:1065-76. 2004
    ..Here we review the molecular basis of thrombin allostery as recently emerged from mutagenesis and structural studies. The role of Na+ in blood coagulation and the evolution of serine proteases are also discussed...
  2. ncbi request reprint A structural perspective on enzymes activated by monovalent cations
    Enrico Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 281:1305-8. 2006
    ..That enables a simple classification of these functionally diverse enzymes and reveals unanticipated connections with ion transporters...
  3. ncbi request reprint Thrombin allostery
    Enrico Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    Phys Chem Chem Phys 9:1291-306. 2007
    ..The molecular mechanism of thrombin allostery is a remarkable example of long-range communication that offers a paradigm for many other biological systems...
  4. pmc Serine proteases
    Enrico Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110, USA
    IUBMB Life 61:510-5. 2009
    ..A new paradigm emerges where two forms of the protease, E* and E, are in allosteric equilibrium and determine biological activity and specificity...
  5. ncbi request reprint Thrombin as procoagulant and anticoagulant
    E Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University Medical School, St Louis, MO 63110, USA
    J Thromb Haemost 5:196-202. 2007
    ..Thrombin mutants with selectively compromised activity toward fibrinogen and PAR1 are effective in vivo as anticoagulant and antithrombotic agents...
  6. pmc Thrombin
    Enrico Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University Medical School, St Louis, MO 63110, United States
    Mol Aspects Med 29:203-54. 2008
    ..Thrombin is now looked upon as a model system for the quantitative analysis of biologically important enzymes...
  7. pmc Theory of allosteric effects in serine proteases
    E Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Biophys J 70:174-81. 1996
    ..Analysis of the allosteric changes in thrombin activity induced by thrombomodulin and Na+ in terms of this equation yields accurate determinations of the equilibrium binding constants for both effectors...
  8. ncbi request reprint Determinants of specificity in coagulation proteases
    M J Page
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Thromb Haemost 3:2401-8. 2005
    ..We also draw attention to a functional polarity that exists in the serine protease fold, which sheds light on the structural linkages between the active site and exosites...
  9. ncbi request reprint Molecular mechanisms of thrombin function
    E Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell Mol Life Sci 53:701-30. 1997
    ..All vitamin K-dependent proteases and some complement factors are subject to the Na(+)-dependent regulation discovered for thrombin. Na+ is therefore a key factor in the activation of zymogens in the coagulation and complement systems...
  10. pmc Na+ binding to meizothrombin desF1
    M E Papaconstantinou
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell Mol Life Sci 65:3688-97. 2008
    ..Evidence that meizothrombin exists in multiple conformations provides valuable new information for studies of the mechanism of prothrombin activation...
  11. ncbi request reprint Determinants of thrombin specificity
    E Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 S Euclid Avenue, Box 8231, St Louis, MO 63110, USA
    Ann N Y Acad Sci 936:133-46. 2001
    ..It is now possible to extend this strategy to the study of other interactions of thrombin, as well as to related serine proteases...
  12. ncbi request reprint Residue Asp-189 controls both substrate binding and the monovalent cation specificity of thrombin
    Swati Prasad
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 279:10103-8. 2004
    ....
  13. pmc Mutant N143P reveals how Na+ activates thrombin
    Weiling Niu
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 284:36175-85. 2009
    ..Absolute conservation of the 143-192 H-bond in trypsin-like proteases and the importance of the oxyanion hole in protease function suggest that this mechanism of Na(+) activation is present in all Na(+)-activated trypsin-like proteases...
  14. ncbi request reprint Structural basis of Na+ activation mimicry in murine thrombin
    Francesca Marino
    Department of Biochemistry and Molecular Biophysics, Washington University Medical School, St Louis, Missouri 63110, USA
    J Biol Chem 282:16355-61. 2007
    ..The molecular strategy of Na+ activation mimicry unraveled for murine thrombin is relevant to serine proteases and enzymes activated by monovalent cations in general...
  15. ncbi request reprint Replacement of thrombin residue G184 with Lys or Arg fails to mimic Na+ binding
    D B Roy
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA
    Proteins 43:315-8. 2001
    ..These findings demonstrate that Na+ binding to thrombin is difficult to mimic functionally with residue side-chains, in analogy with results from other systems...
  16. doi request reprint Serine peptidases: classification, structure and function
    M J Page
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell Mol Life Sci 65:1220-36. 2008
    ....
  17. ncbi request reprint Molecular mapping of thrombin-receptor interactions
    Y M Ayala
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA
    Proteins 45:107-16. 2001
    ..3D models of thrombin complexed with PAR1, PAR3, and PAR4 are constructed and account for the perturbations documented by the mutagenesis studies...
  18. ncbi request reprint Energetic and structural consequences of perturbing Gly-193 in the oxyanion hole of serine proteases
    Kevin M Bobofchak
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:25644-50. 2005
    ..5 kcal/mol but < 3.0 kcal/mol. These results shed light on a basic aspect of the enzyme-substrate interaction in the entire family of trypsin-like serine proteases...
  19. ncbi request reprint Crystal structure of thrombin in a self-inhibited conformation
    Agustin O Pineda
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    J Biol Chem 281:32922-8. 2006
    ..These findings demonstrate that thrombin may assume an inactive conformation in the absence of Na(+) and that its procoagulant and anticoagulant activities are closely linked to the mobility of residue 215...
  20. pmc Redesigning the monovalent cation specificity of an enzyme
    Swati Prasad
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 100:13785-90. 2003
    ..The conversion, however, does not result into a K+-activated enzyme...
  21. ncbi request reprint High resolution crystal structures of free thrombin in the presence of K(+) reveal the molecular basis of monovalent cation selectivity and an inactive slow form
    Christopher J Carrell
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110, USA
    Biophys Chem 121:177-84. 2006
    ..This form, named S(*), corresponds to the inactive Na(+)-free slow form identified by early kinetic studies. A simple model of thrombin allostery that incorporates the contribution of S(*) is proposed...
  22. pmc Stabilization of the E* form turns thrombin into an anticoagulant
    Alaji Bah
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 284:20034-40. 2009
    ....
  23. pmc Role of the A chain in thrombin function
    M E Papaconstantinou
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110, USA
    Cell Mol Life Sci 65:1943-7. 2008
    ....
  24. ncbi request reprint Thrombomodulin changes the molecular surface of interaction and the rate of complex formation between thrombin and protein C
    Hong Xu
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:7956-61. 2005
    ....
  25. ncbi request reprint The anticoagulant thrombin mutant W215A/E217A has a collapsed primary specificity pocket
    Agustin O Pineda
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 279:39824-8. 2004
    ....
  26. ncbi request reprint Important role of the cys-191 cys-220 disulfide bond in thrombin function and allostery
    Leslie A Bush-Pelc
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    J Biol Chem 282:27165-70. 2007
    ..In addition, the disulfide bond stabilizes the 186 and 220 loops that are critical for Na+ binding and activation...
  27. ncbi request reprint Role of Na+ and K+ in enzyme function
    Michael J Page
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    Physiol Rev 86:1049-92. 2006
    ..From this analysis, M+ complexation has the potential to be an efficient regulator of enzyme catalysis and stability and offers novel strategies for protein engineering to improve enzyme function...
  28. pmc Engineering protein allostery: 1.05 A resolution structure and enzymatic properties of a Na+-activated trypsin
    Michael J Page
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110, USA
    J Mol Biol 378:666-72. 2008
    ..The results demonstrate that trypsin can be engineered into an efficient allosteric protease, and that Na(+) activation is interwoven with substrate selectivity in the trypsin scaffold...
  29. ncbi request reprint Thrombin interactions
    Enrico Di Cera
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    Chest 124:11S-7S. 2003
    ..The functional versatility of thrombin owes much to its evolutionary origin and results from structural determinants and mechanisms that can be exploited by pharmacologic intervention...
  30. ncbi request reprint Mutation of W215 compromises thrombin cleavage of fibrinogen, but not of PAR1 or protein C
    Y M Ayala
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St. Louis, MO 63110, USA
    Ann N Y Acad Sci 936:456-8. 2001
    ..The environment of W215 influences differentially three physiologically important interactions of thrombin, a feature that should assist in the separate study of each of these functions in vivo...
  31. pmc Unexpected crucial role of residue 225 in serine proteases
    E R Guinto
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 96:1852-7. 1999
    ..These findings have broad implications in the rational design of enzymes with enhanced catalytic properties...
  32. pmc Molecular markers of serine protease evolution
    M M Krem
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110-1093, USA
    EMBO J 20:3036-45. 2001
    ..A genetic mechanism for mutation of conserved markers, domain duplication followed by gene splitting, is suggested by analysis of evolutionary markers from newly sequenced genes with multiple protease domains...
  33. ncbi request reprint Crystal structure of the anticoagulant slow form of thrombin
    Agustin O Pineda
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    J Biol Chem 277:40177-80. 2002
    ..The structure of the slow form explains the reduced specificity toward synthetic and natural substrates and suggests a molecular basis for its anticoagulant properties...
  34. ncbi request reprint The thrombin epitope recognizing thrombomodulin is a highly cooperative hot spot in exosite I
    Agustin O Pineda
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 277:32015-9. 2002
    ..Finally, the Ala substitution of two negatively charged residues in exosite II, Asp(100) and Asp(178), is found unexpectedly to significantly increase thrombomodulin binding...
  35. pmc Structural identification of the pathway of long-range communication in an allosteric enzyme
    Prafull S Gandhi
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 105:1832-7. 2008
    ..The crystal structure of the thrombin-PAR1 complex, solved at 2.2-A resolution, reveals the details of this long-range allosteric communication in terms of a network of polar interactions...
  36. ncbi request reprint Three-dimensional models of proteases involved in patterning of the Drosophila Embryo. Crucial role of predicted cation binding sites
    Thierry Rose
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 278:11320-30. 2003
    ..A mutation in Ea predicted to introduce Na(+) binding results in apparently increased activity with ventralization of the embryo, an effect not observed with wild-type Ea mRNA...
  37. ncbi request reprint Murine thrombin lacks Na+ activation but retains high catalytic activity
    Leslie A Bush
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    J Biol Chem 281:7183-8. 2006
    ..Murine thrombin can also cleave substrates carrying Phe at P1, which potentially broadens the repertoire of molecular targets available to the enzyme in vivo...
  38. ncbi request reprint Rapid kinetics of Na+ binding to thrombin
    Alaji Bah
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 281:40049-56. 2006
    ..These findings elucidate the mechanism of Na(+) binding to thrombin and are relevant to other clotting factors and enzymes allosterically activated by monovalent cations...
  39. ncbi request reprint Molecular dissection of Na+ binding to thrombin
    Agustin O Pineda
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 279:31842-53. 2004
    ..The role of the water network uncovered in this study establishes a new paradigm for the allosteric regulation of thrombin and other Na(+)-activated enzymes involved in blood coagulation and the immune response...
  40. ncbi request reprint Crystal structure of the thrombin mutant D221A/D222K: the Asp222:Arg187 ion-pair stabilizes the fast form
    Agustin O Pineda
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110, USA
    Biophys Chem 112:253-6. 2004
    ..These findings reinforce the crucial role of the Asp222:Arg187 ion-pair in stabilizing the fast form of thrombin...
  41. ncbi request reprint Hirudin binding reveals key determinants of thrombin allostery
    Kristen E Mengwasser
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:26997-7003. 2005
    ..Remarkably, no correlation is found between the energetic and structural involvements of thrombin residues in hirudin recognition, which invites caution in the analysis of protein-protein interactions in general...
  42. pmc Cl- regulates the structure of the fibrin clot
    E Di Stasio
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Biophys J 75:1973-9. 1998
    ..This discovery opens new possibilities for the design of molecules that can specifically modify the clot structure by targeting the structural domains responsible for Cl- binding to fibrin...
  43. pmc Crystal structures of murine thrombin in complex with the extracellular fragments of murine protease-activated receptors PAR3 and PAR4
    Alaji Bah
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 104:11603-8. 2007
    ....
  44. pmc Mechanism of the anticoagulant activity of thrombin mutant W215A/E217A
    Prafull S Gandhi
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 284:24098-105. 2009
    ..The E* --> E transition requires the combined binding of thrombomodulin and protein C and restores activity of the mutant WE in the anticoagulant pathway...
  45. ncbi request reprint Substrate recognition drives the evolution of serine proteases
    Thierry Rose
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 277:19243-6. 2002
    ....
  46. ncbi request reprint Thrombin functions through its RGD sequence in a non-canonical conformation
    Matthew E Papaconstantinou
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:29393-6. 2005
    ....
  47. ncbi request reprint Evolution of enzyme cascades from embryonic development to blood coagulation
    Maxwell M Krem
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110 1093, USA
    Trends Biochem Sci 27:67-74. 2002
    ..Extensive similarities suggest that these cascades were built by adding enzymes from the bottom of the cascade up and from similar macromolecular building blocks...
  48. ncbi request reprint Three-dimensional modeling of thrombin-fibrinogen interaction
    Thierry Rose
    Department of Biochemistry, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 277:18875-80. 2002
    ..The three-dimensional models suggest a possible pattern of recognition by thrombin that applies generally to other natural substrates...
  49. ncbi request reprint Ser(214) is crucial for substrate binding to serine proteases
    Maxwell M Krem
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    J Biol Chem 277:40260-4. 2002
    ..The S214C mutant is catalytically inactive, which suggests that during evolution the TCN-->AGY codon transitions for Ser(214) occurred through Thr intermediates...
  50. pmc Engineering thrombin for selective specificity toward protein C and PAR1
    Francesca Marino
    Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, Missouri 63104, USA
    J Biol Chem 285:19145-52. 2010
    ..Mutations of Trp(215) provide important reagents for dissecting the multiple functional roles of thrombin in the blood and for clinical applications...
  51. pmc Crystal structure of thrombin bound to the uncleaved extracellular fragment of PAR1
    Prafull S Gandhi
    Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St Louis, Missouri 63104, USA
    J Biol Chem 285:15393-8. 2010
    ..The results fill a significant gap in our understanding of the molecular mechanisms of recognition by thrombin in ways that are relevant to other physiological substrates...
  52. ncbi request reprint Dissecting substrate recognition by thrombin using the inactive mutant S195A
    Maxwell M Krem
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, MO 63110, USA
    Biophys Chem 100:315-23. 2003
    ..These findings demonstrate that inactive mutants of enzymes make it possible to dissect the equilibrium components linked to substrate binding and complement information on the kinetic properties of the wild type...
  53. ncbi request reprint Conversion of trypsin into a Na(+)-activated enzyme
    Michael J Page
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St Louis, Missouri 63110, USA
    Biochemistry 45:2987-93. 2006
    ....
  54. ncbi request reprint Characterization of the bacterial sensor protein PhoQ. Evidence for distinct binding sites for Mg2+ and Ca2+
    E G Véscovi
    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 272:1440-3. 1997
    ..Cumulatively, these experiments demonstrate that Mg2+ can bind to the sensing domain of PhoQ and establish the presence of distinct binding sites for Mg2+ and Ca2+ in the PhoQ protein...
  55. pmc Evolution of peptidase diversity
    Michael J Page
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 283:30010-4. 2008
    ..These findings provide a framework for deeper investigation into the evolutionary forces that shaped each peptidase family and a roadmap to develop a timeline for their expansion as an interconnected system...
  56. ncbi request reprint Allosteric effects potentiating the release of the second fibrinopeptide A from fibrinogen by thrombin
    John R Shainoff
    Department of Chemistry, Cleveland State University, Cleveland, Ohio 44115, USA
    J Biol Chem 277:19367-73. 2002
    ....
  57. ncbi request reprint Discovery of potent, selective, orally active, nonpeptide inhibitors of human mast cell chymase
    Michael N Greco
    Research and Early Development, Johnson and Johnson Pharmaceutical Research and Development, Spring House, Pennsylvania 19477 0776, USA
    J Med Chem 50:1727-30. 2007
    ..Compound 5f was selective for inhibiting chymase versus eight serine proteases. Compound 6h was orally bioavailable in rats (F=39%), and orally efficacious in a hamster model of inflammation...
  58. ncbi request reprint Is Na+ a coagulation factor?
    Michael J Page
    Thromb Haemost 95:920-1. 2006
  59. ncbi request reprint Crystal structure of thrombin in complex with fibrinogen gamma' peptide
    Agustin O Pineda
    Biophys Chem 125:556-9. 2007
    ..These findings are consistent with functional data and broaden our understanding of how thrombin interacts with fibrinogen at the molecular level...
  60. ncbi request reprint The conformation of the activation peptide of protein C is influenced by Ca2+ and Na+ binding
    Likui Yang
    Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri 63104, USA
    J Biol Chem 279:38519-24. 2004
    ..Activation of the mutant protein C by chymotrypsin proceeds at a rate comparable to the activation of wild-type protein C by the thrombin-thrombomodulin complex...
  61. pmc Engineering protease specificity made simple, but not simpler
    Enrico Di Cera
    Nat Chem Biol 4:270-1. 2008
  62. ncbi request reprint Thrombin mutant W215A/E217A acts as a platelet GPIb antagonist
    Michelle A Berny
    Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA
    Arterioscler Thromb Vasc Biol 28:329-34. 2008
    ..The aim of this study was to delineate the molecular mechanism of direct WE-platelet interactions under static and shear conditions...
  63. pmc Mechanism of Na(+) binding to thrombin resolved by ultra-rapid kinetics
    Stefano Gianni
    Istituto di Biologia e Patologia Molecolari del CNR, Dipartimento di Scienze Biochimiche, Universita di Roma La Sapienza, Rome, Italy
    Biophys Chem 131:111-4. 2007
    ....
  64. ncbi request reprint The thrombin mutant W215A/E217A shows safe and potent anticoagulant and antithrombotic effects in vivo
    Andras Gruber
    Department of Biomedical Engineering and Yerkes Regional Primate Research Center, Emory University School of Medicine and Georgia Institute of Technology, Atlanta, Georgia 30322, USA
    J Biol Chem 277:27581-4. 2002
    ..These results show that engineered thrombin derivatives that selectively activate protein C may represent useful therapeutic agents for the treatment of thrombotic disorders...
  65. pmc Relative antithrombotic and antihemostatic effects of protein C activator versus low-molecular-weight heparin in primates
    Andras Gruber
    Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Avenue, Portland, OR 97239, USA
    Blood 109:3733-40. 2007
    ..Our data suggest that limited pharmacological protein C activation might exhibit considerable thrombosis specificity...
  66. pmc Studies on the basis for the properties of fibrin produced from fibrinogen-containing gamma' chains
    Kevin R Siebenlist
    Department of Biomedical Sciences, College of Health Sciences, Marquette University, Schroeder Health Complex, 426, PO Box 1881, Milwaukee, WI 53233 1881, USA
    Blood 106:2730-6. 2005
    ..Fourth, fibrinolysis of fibrin 2 was delayed compared with fibrin 1. Altogether, differences between the structure and function of fibrins 1 and 2 are attributable to the effects of thrombin binding to gamma' chains...
  67. ncbi request reprint Protective signaling by activated protein C is mechanistically linked to protein C activation on endothelial cells
    Clemens Feistritzer
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 281:20077-84. 2006
    ..WE may have powerful protective effects in systemic inflammation through signaling by the endogenously generated APC...
  68. ncbi request reprint Atherosclerosis: testing the water
    Enrico Di Cera
    Arterioscler Thromb Vasc Biol 23:1713-4. 2003
  69. ncbi request reprint A novel, potent dual inhibitor of the leukocyte proteases cathepsin G and chymase: molecular mechanisms and anti-inflammatory activity in vivo
    Lawrence de Garavilla
    Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, Spring House, Pennsylvania 19477 0776, USA
    J Biol Chem 280:18001-7. 2005
    ..These findings demonstrate that it is possible to inhibit both cathepsin G and chymase with a single molecule and suggest an exciting opportunity in the treatment of asthma and chronic obstructive pulmonary disease...