The 2.8 Å crystal structure of Gla-domainless activated protein C

EMBO Journal

Volumn 15, Issue 24, 1996, Pages 6822-6831

  Mather, Timothy ^a   Oganessyan, Vaheh ^a   Hof, Peter ^a   Huber, Robert ^a   Foundling, Steven ^b   Esmon, Charles ^b,c   Bode, Wolfram ^a  

^a MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

^b Oklahoma Medical Research Institute   (United States)

^c HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

Anticoagulant; Coagulation; Crystal structure; Protein C; Serine protease

Indexed keywords

ACTIVATED PROTEIN C; ANION; ANTICOAGULANT AGENT; BLOOD CLOTTING FACTOR 10A; DISULFIDE; EPIDERMAL GROWTH FACTOR; THROMBIN; TRYPSIN; PROTEIN C;

ARTICLE; BINDING SITE; CALCIUM BINDING; CONTROLLED STUDY; CRYSTAL STRUCTURE; DISULFIDE BOND; ENZYME ACTIVE SITE; HUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; CATALYSIS; CHEMISTRY; METABOLISM; PROTEIN CONFORMATION; PROTEIN FOLDING; X RAY CRYSTALLOGRAPHY;

BINDING SITES; CATALYSIS; CRYSTALLOGRAPHY, X-RAY; HUMANS; PROTEIN C; PROTEIN CONFORMATION; PROTEIN FOLDING;

EID: 0030468098     PISSN: 02614189     EISSN: None     Source Type: Journal    
DOI: 10.1002/j.1460-2075.1996.tb01073.x     Document Type: Article

References (62)

1. Bertina,R.M., Koeleman,B.P.C., Kostar,T., Rosendaal,F.R., Dirven,R.J., de Ronde,H., van der Velden,P.A. and Reitsma,P.H. (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature, 369, 64-67.
2. Bode,W. and Huber,R. (1992) Natural protein proteinase inhibitors and their interaction with proteases. Eur. J. Biochem., 204, 433-451.
3. Bode,W. and Schwager,P. (1975) The refined crystal structure of bovine β-trypsin at 1.8 Å resolution. II. Cristallographie refinement, calcium binding site, benzamidine binding site and active site at pH 7. J. Mol. Biol., 98, 693-717.
4. Bode,W., Mayr,I., Baumann,U., Huber,R., Stone,S.R. and Hofsteenge,J. (1989) The refined 1.9 A crystal structure of human α-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J., 8, 3467-3475.
5. Bode,W., Turk,D. and Karshikov,A. (1992) The refined 1.9 Å X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human alpha-thrombin: structure analysis, overall structure, electrostatic properties, detailed active site geometry and structure-function relationships. Protein Sci., 1, 426-471.
6. Brandstetter,H. (1995) Röntgenkristallographische Untersuchungen an Enzymen des Blutgerinnungssystems. Ph.D. Thesis, Technische Universität, München, Germany.
7. Brandstetter,H., Bauer,M., Huber,R., Lollar,P. and Bode,W. (1995) X-ray structure of clotting factor IXa: active site and module structure related to Xase activity and hemophilia B. Proc. Natl Acad. Sci. USA, 92, 9796-9800.
8. Bruenger,A.T. (1992) XPLOR, Version 3.1. A System for X-Ray Crystallography and NMR. Yale University Press, New Haven, CT.
9. Comp,P.C. (1986) Hereditary disorders predisposing to thrombosis. In B.Coller (ed.), Progress in Hemostasis and Thrombosis. Grune and Stratton, Orlando FL, USA, Vol. 8, pp. 71-102.
10. Comp,P.C. and Esmon,C.T. (1981) Generation of fibrinolytic activity by infusion of activated protein C in dogs. J. Clin. Invest., 68, 1221-1228.
11. Dahlbäck,B. (1995) Thrombophilia: the discovery of activated protein C resistance. Adv. Genet., 33, 135-175.
12. D'Souza,S.E., Ginsberg,M.H. and Plow,E.F. (1991) Arginyl-glycylaspartic acid (RGD): a cell adhesion motif. Trends Biochem. Sci., 16, 246-250.
13. Esmon,C.T. (1989) The roles of protein C and thrombomodulin in the regulation of blood coagulation. J. Biol. Chem., 264, 4743-4746.
14. Esmon,C.T. (1995) Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface. FASEB J., 9, 946-955.
15. Esmon,N.L, DeBault,L.E. and Esmon,C.T. (1983) Proteolytic formation and properties of γ-carboxy glutamic acid-domainless protein C. J. Biol. Chem., 258, 5548-5553.
16. Esmon,C.T., Taylor,F.J. and Snow,T.R. (1991) Inflammation and coagulation: linked processes potentially regulated through a common pathway mediated by protein C. Thromb. Haemostasis, 66, 160-165.
17. Esmon,C.T., Esmon,N.L., Le Bonniec,B.F. and Johnson,A.E. (1993) Protein C activation. Methods Enzymol., 222, 359-385.
18. Evans,S.V. (1993) SETOR: Hardware lighted three-dimensional solid model representations of macromolecules. J. Mol. Graphics, 11, 134-138.
19. Fay,P.J., Smudzin,T.M. and Walker,F.J. (1991) Activated protein-C catalyzed inactivation of human factor VIII and factor Villa. J. Biol. Chem., 266, 20139-20145.
20. Fernlund,P. and Stenflo,J. (1982) Amino acid sequence of the light chain of bovine protein C. J. Biol. Chem., 257, 12170-12179.
21. Foster,D. and Davie,E.W. (1984) Characterization of a cDNA coding for human protein C. Proc. Natl Acad. Sci. USA, 81, 4766-4770.
22. Foster,D.C., Yoshitake,S. and Davie,E.W. (1985) The nucleotide sequence of the gene for human protein C. Proc. Natl Acad. Sci. USA, 82, 4673-4677.
23. Fukudome,K. and Esmon,C.T. (1994) Identification, cloning and regulation of a novel endothelial cell protein C/activated protein C receptor. J. Biol. Chem., 269, 26486-26491.
24. Griffith,M.J. (1982) Kinetics of the heparin-enhanced antithrombin III/ thrombin reaction. Evidence for a template model for the mechanism of action of heparin. J. Biol. Chem., 257, 7360-7365.
25. Grinnell,B.W., Walls,J.D. and Gerlitz,B. (1991) Glycosylation of human protein C affects its secretion, processing, functional activities and activation by thrombin. J. Biol. Chem., 266, 9778-9785.
26. Grinnell,B.W., Hermann,R.B. and Yan,S.B. (1994) Human protein C inhibits selectin-mediated cell adhesion: role of unique fucosylated oligosaccharide. Glycobiology, 4, 221-226.
27. Guinto,E.G., Ye,J., Le Bonniec,B.F. and Esmon,C.T. (1994) Glu192→Gln substitution in thrombin yields an enzyme that is effectively inhibited by bovine pancreatic trypsin inhibitor and tissue factor pathway inhibitor. J. Biol. Chem., 269, 18395-18400.
28. Heeb,M.J., Gruber,A. and Griffin,J.H. (1991) Identification of divalent metal ion-dependent inhibition of activated protein C by alpha-2-macroglobulin and alpha-2-antiplasmin in blood and comparisons to inhibition of factor Xa, thrombin and plasmin. J. Biol. Chem., 266, 17606-17612.
29. Hermans,J.M. and Stone,S.R. (1993) Interaction of activated protein C with serpins. Biachem. J., 295, 239-245.
30. Holly,R. and Foster,D.C. (1994) Resistance to inhibition by alpha-1-anti-trypsin and species specificity of a chimeric human/bovine protein C. Biochemistry, 33, 1876-1880.
31. Ichinose,A. and Davie,E.W. (1994) The blood coagulation factors: their cDNAs, genes and expression. In Coleman,R.W., Hirsh,J., Marder,V.J. and Salzman,E.W. (eds), Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd edn. J.B.Lippincott Company, Philadelphia, PA, pp. 19-54.
32. Kalafatis,M., Rand,M.D. and Mann,K.G. (1994) The mechanism of inactivation of human factor V and human factor Va by activated protein C. J. Biol. Chem., 269, 31869-31880.
33. Laskowski,R.A., MacArthur,M.W., Moss,D.S. and Thornton,J.M. (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Crystalhgr., 26, 283-291.
34. Le Bonniec,B.F. and Esmon,C.T. (1991) Glu-192→Gln substitution in thrombin mimics the catalytic switch induced by thrombomodulin. Proc. Natl Acad. Sci. USA, 88, 7371-7375.
35. Mammen,E.F., Thomas,W.R. and Seegers,W.H. (1960) Activation of purified prothrombin to autoprothrombin or autoprothrombin II (platelet cofactor II) or autoprothrombin II-a. Thromb. Diath. Haemorrh., 5, 218-249.
36. Marler,R.A. and Neumann,A. (1990) Neonatal purpura fulminans due to homozygous protein C or protein S deficiency. Semin. Thromb. Hemostasis, 16, 299-309.
37. Mesters,R.M., Houghten,R.A. and Griffin,J.H. (1991) Identification of a sequence of human activated protein C (residues 390-404) essential for its anticoagulant activity. J. Biol. Chem., 266, 24514-24519.
38. Mesters,R.M, Heeb,M.J. and Griffin,J.H. (1993a) Interactions and inhibition of blood coagulation factor Va involving residues 311-325 of activated protein C. Protein Sci., 2, 1482-1489.
39. Mesters,R.M, Heeb,M.J. and Griffin,J.H. (1993b) A novel exosite in the light chain of human activated protein C essential for interaction with blood coagulation factor Va. Biochemistry, 32, 12656-12663.
40. Murakawa,M., Okamura,T., Kamura,T., Kuroiwa,M., Harada,M. and Niho,Y. (1994) A comparative study of partial primary structures of the catalytic region of mammalian protein C. Br. J. Haematol., 86, 590-600.
41. Navaza,J. (1994) AMoRe: an automated package for molecular replacement. Acta Crystallogr., A50, 157-163.
42. Neuenschwander,P.F. and Morrissey,J.H. (1995) Alteration of the substrate and inhibitor specificities of blood coagulation factor VIIa: importance of amino acid residue K192. Biochemistry, 34, 8701-8707.
43. Otwinowski,Z. (1993) DENZO: An Oscillation Data Processing Program for Protein Crystallography. Yale University, New Haven, CT.
44. Padmanabhan,K., Padmanabhan,K.P., Tulinsky,A., Park,C.H., Bode,W., Huber,R., Blankenship,D.T., Cardin,A.D. and Kisiel,W. (1993) Structure of Des(1-45) factor Xa at 2.2 Å resolution. J. Mol. Biol., 232, 947-966.
45. Pratt,C.W., Whinna,H.C. and Church,F.C. (1992) A comparison of three heparin-binding serine protease inhibitors. J. Biol. Chem., 267, 8795-8801.
46. Reitsma,P.H. et al. (1995) Protein C deficiency: a database of mutations, 1995 update. Thromb. Haemostasis, 73, 876-889.
47. Rezaie,A.R. and Esmon,C.T. (1993) Conversion of glutamic acid 192 to glutamine in activated protein C changes the substrate specificity and increases reactivity toward macromolecular inhibitors. J. Biol. Chem., 268, 19943-19948.
48. Rezaie,A.R. and Esmon,C.T. (1995a) Contribution of residue 192 in factor Xa to enzyme specificity and function. J. Biol. Chem., 270, 16176-16181.
49. 2+-dependent conformational change required for activation by the thrombin-thrombomodulin complex. Biochemistry, 34, 12221-12226.
50. 2+ for rapid activation by the thrombin-thrombomodulin complex. J. Biol. Chem., 269, 3151-3154.
51. Rivard,G.E., David,M., Farrell,C. and Schwarz,H.P. (1995) Treatment of purpura fulminans in meningococcemia with protein C concentrate. J. Pediatr., 126, 646-652.
52. Sakata,Y., Curriden,S., Lawrence,D., Griffin,J.H. and Loskutoff,D.J. (1985) Activated protein C stimulates the fibrinolytic activity of cultured endothelial cells and decreases antiactivator activity. Proc. Natl Acad. Sci. USA, 82, 1121-1125.
53. Sander,C. and Schneider,R. (1991) Database of homology-deri ved protein structures Proteins, 9, 56-68.
54. Schlechter,I., and Berger,A. (1967) On the size of the active site in proteases. I. Papain. Biochem. Biophys. Res. Commun., 27, 157-162.
55. Scully,M.F., Toh,C.H, Hoogendoom,H., Manuel,R.P., Nesheim,M.E., Solymoss,S. and Giles,A.R. (1993). Activation of protein C and its distribution between its inhibitors, protein C inhibitor, alpha-1-antitrypsin and alpha-2-macroglobulin in patients with disseminated intravascular coagulation. Thromb. Haemostasia, 69, 448-453.
56. Seegers,W.H., Novoa,E., Henry,R.L. and Hassouna,H.I. (1976) Relationship of 'new' vitamin K-dependent protein C and 'old' autoprothrotnbin II-a. Thromb. Res., 8, 543-552.
57. Stenflo,J. (1976) A new vitamin K-dependent protein. J. Biol. Chem., 251, 355-363.
58. Stenflo,J. and Fernlund,P. (1982) Amino acid sequence of the heavy chain of bovine protein C. J. Biol. Chem., 257, 12180-12190.
59. Stone,S.R. and Hofsteenge,J. (1985) Specificity of activated human protein C. Biochem. J., 230, 497-502.
60. Turk,D. (1992) Weiterentwicklung eines Programms für Molekülgraphik und Elektronendichte - Manipulation und seine Anwendung auf verschiedene Protein-Strukturaufklärungen. Ph.D. Thesis, Technische Universität, München.
61. Vijayalakshmi,J., Padmanabhan,K.P., Mann,K.G. and Tulinsky,A. (1995) The isomorphous structures of prethrombin2, hirugen- and PPACK-thrombin: changes accompanying activation and exosite binding to thrombin. Protein Sci., 3, 2254-2271.
62. Zolton,R.P. and Seegers,W.H. (1973) Autoprothrombin II-A: thrombin removal and mechanism of induction of fibrinolysis. Thromb. Res., 3, 23-33.