Crystal structure of thrombin in complex with s-variegin: Insights of a novel mechanism of inhibition and design of tunable thrombin inhibitors

PLoS ONE

Volumn 6, Issue 10, 2011, Pages

  Koh, Cho Yeow ^a   Kumar, Sundramurthy ^a   Kazimirova, Maria ^b   Nuttall, Patricia A ^c   Radhakrishnan, Uvaraj P ^d   Kim, Seongcheol ^d   Jagadeeswaran, Pudur ^d   Imamura, Takayuki ^e   Mizuguchi, Jun ^e   Iwanaga, Sadaaki ^e   Swaminathan, Kunchithapadam ^a   Kini, R Manjunatha ^a,f  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b INSTITUTE OF CHEMISTRY   (Slovakia)

^c CENTRE FOR ECOLOGY AND HYDROLOGY   (United Kingdom)

^d UNIVERSITY OF NORTH TEXAS   (United States)

^e Kaketsuken   (Japan)

^f VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HIRULOG; S VARIEGIN; THROMBIN; THROMBIN INHIBITOR; UNCLASSIFIED DRUG; VARIEGIN DERIVATIVE; ANTITHROMBIN; HIRUDIN DERIVATIVE; HIRUGEN; MUTANT PROTEIN; PEPTIDE; PEPTIDE FRAGMENT; SALIVA PROTEIN; VARIEGIN PROTEIN, AMBLYOMMA VARIEGATUM;

ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; BINDING SITE; COMPETITIVE INHIBITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG MECHANISM; DRUG POTENCY; EMBRYO; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LARVA; NONHUMAN; PHARMACOKINETICS; PROTEIN STRUCTURE; ZEBRA FISH; AMINO ACID SEQUENCE; ANIMAL; BIOCATALYSIS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; KINETICS; METABOLISM; MOLECULAR GENETICS; STATIC ELECTRICITY; X RAY CRYSTALLOGRAPHY;

AMBLYOMMA HEBRAEUM;

AMINO ACID SEQUENCE; ANIMALS; ANTITHROMBINS; BINDING SITES; BIOCATALYSIS; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; HIRUDINS; HUMANS; KINETICS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTANT PROTEINS; PEPTIDE FRAGMENTS; PEPTIDES; SALIVARY PROTEINS AND PEPTIDES; STATIC ELECTRICITY; THROMBIN; ZEBRAFISH;

EID: 80055037344     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0026367     Document Type: Article

References (58)

1. Huntington JA, (2005) Molecular recognition mechanisms of thrombin. J Thromb Haemost 3: 1861-1872.
2. Bode W, Turk D, Karshikov A, (1992) The refined 1.9-A 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.
3. Rydel TJ, Tulinsky A, Bode W, Huber R, (1991) Refined structure of the hirudin-thrombin complex. J Mol Biol 221: 583-601.
4. Skrzypczak-Jankun E, Carperos VE, Ravichandran KG, Tulinsky A, Westbrook M, et al. (1991) Structure of the hirugen and hirulog 1 complexes of alpha-thrombin. J Mol Biol 221: 1379-1393.
5. Huntington JA, (2008) How Na+ activates thrombin-a review of the functional and structural data. Biol Chem 389: 1025-1035.
6. Lane DA, Philippou H, Huntington JA, (2005) Directing thrombin. Blood 106: 2605-2612.
7. Koh CY, Kini RM, (2008) Anticoagulants from hematophagous animals. Expert Rev Hematol 1: 135-139.
8. Ajjan R, Grant PJ, (2006) Coagulation and atherothrombotic disease. Atherosclerosis 186: 240-259.
9. Gross PL, Weitz JI, (2008) New anticoagulants for treatment of venous thromboembolism. Arterioscler Thromb Vasc Biol 28: 380-386.
10. Greinacher A, Warkentin TE, (2008) The direct thrombin inhibitor hirudin. Thromb Haemost 99: 819-829.
11. Warkentin TE, Greinacher A, Koster A, (2008) Bivalirudin. Thromb Haemost 99: 830-839.
12. Yeh RW, Jang IK, (2006) Argatroban: update. Am Heart J 151: 1131-1138.
13. Eriksson BI, Smith H, Yasothan U, Kirkpatrick P, (2008) Dabigatran etexilate. Nat Rev Drug Discov 7: 557-558.
14. Champagne DE, (2004) Antihemostatic strategies of blood-feeding arthropods. Curr Drug Targets Cardiovasc Haematol Disord 4: 375-396.
15. Koh CY, Kini RM, (2009) Molecular diversity of anticoagulants from haematophagous animals. Thromb Haemost 102: 437-453.
16. Koh CY, Kazimirova M, Trimnell A, Takac P, Labuda M, et al. (2007) Variegin, a novel fast and tight binding thrombin inhibitor from the tropical bont tick. J Biol Chem 282: 29101-29113.
17. Koh CY, Kazimirova M, Nuttall PA, Kini RM, (2009) Noncompetitive inhibitor of thrombin. Chembiochem 10: 2155-2158.
18. Yonemura H, Imamura T, Soejima K, Nakahara Y, Morikawa W, et al. (2004) Preparation of recombinant alpha-thrombin: high-level expression of recombinant human prethrombin-2 and its activation by recombinant ecarin. J Biochem (Tokyo) 135: 577-582.
19. Soejima K, Mimura N, Yonemura H, Nakatake H, Imamura T, et al. (2001) An efficient refolding method for the preparation of recombinant human prethrombin-2 and characterization of the recombinant-derived alpha-thrombin. J Biochem (Tokyo) 130: 269-277.
20. Otwinowski Z, Minor W, (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods in Enzymology 276: 307-326.
21. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, et al. (2007) Phaser crystallographic software. J Appl Crystallogr 40: 658-674.
22. Qiu X, Padmanabhan KP, Carperos VE, Tulinsky A, Kline T, et al. (1992) Structure of the hirulog 3-thrombin complex and nature of the S′ subsites of substrates and inhibitors. Biochemistry 31: 11689-11697.
23. Emsley P, Cowtan K, (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60: 2126-2132.
24. Murshudov GN, Vagin AA, Dodson EJ, (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 53: 240-255.
25. Winn MD, Isupov MN, Murshudov GN, (2001) Use of TLS parameters to model anisotropic displacements in macromolecular refinement. Acta Crystallogr D Biol Crystallogr 57: 122-133.
26. Laskowsi RA, MacArthur MW, Moss DS, Thornton JM, (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26: 283-291.
27. Davis IW, Leaver-Fay A, Chen VB, Block JN, Kapral GJ, et al. (2007) MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res 35: W375-W383.
28. Krissinel E, Henrick K, (2007) Inference of macromolecular assemblies from crystalline state. J Mol Biol 372: 774-797.
29. Bode W, Mayr I, Baumann U, Huber R, Stone SR, et al. (1989) The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J 8: 3467-3475.
30. Jagadeeswaran P, Paris R, Rao P, (2006) Laser-induced thrombosis in zebrafish larvae: a novel genetic screening method for thrombosis. Methods Mol Med 129: 187-195.
31. Liu CC, Brustad E, Liu W, Schultz PG, (2007) Crystal structure of a biosynthetic sulfo-hirudin complexed to thrombin. J Am Chem Soc 129: 10648-10649.
32. Rydel TJ, Ravichandran KG, Tulinsky A, Bode W, Huber R, et al. (1990) The structure of a complex of recombinant hirudin and human alpha-thrombin. Science 249: 277-280.
33. Page MJ, Macgillivray RT, Di Cera E, (2005) Determinants of specificity in coagulation proteases. J Thromb Haemost 3: 2401-2408.
34. Perona JJ, Craik CS, (1995) Structural basis of substrate specificity in the serine proteases. Protein Sci 4: 337-360.
35. Vindigni A, Dang QD, Di Cera E, (1997) Site-specific dissection of substrate recognition by thrombin. Nat Biotechnol 15: 891-895.
36. Stone SR, Hofsteenge J, (1986) Kinetics of the inhibition of thrombin by hirudin. Biochemistry 25: 4622-4628.
37. Dodt J, Kohler S, Baici A, (1988) Interaction of site specific hirudin variants with alpha-thrombin. FEBS Lett 229: 87-90.
38. Braun PJ, Dennis S, Hofsteenge J, Stone SR, (1988) Use of site-directed mutagenesis to investigate the basis for the specificity of hirudin. Biochemistry 27: 6517-6522.
39. Stone SR, Tapparelli C, (1995) Thrombin inhibitors as antithrombotic agents: the importance of rapid inhibition. J Enzyme Inhib 9: 3-15.
40. Fethiere J, Tsuda Y, Coulombe R, Konishi Y, Cygler M, (1996) Crystal structure of two new bifunctional nonsubstrate type thrombin inhibitors complexed with human alpha-thrombin. Protein Sci 5: 1174-1183.
41. Laskowski M Jr, Kato I, (1980) Protein inhibitors of proteinases. Annu Rev Biochem 49: 593-626.
42. Slon-Usakiewicz JJ, Purisima E, Tsuda Y, Sulea T, Pedyczak A, et al. (1997) Nonpolar interactions of thrombin S′ subsites with its bivalent inhibitor: methyl scan of the inhibitor linker. Biochemistry 36: 13494-13502.
43. van de Locht A, Lamba D, Bauer M, Huber R, et al. (1995) Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin. EMBO J 14: 5149-5157.
44. van de Locht A, Stubbs MT, Bode W, Friedrich T, Bollschweiler C, et al. (1996) The ornithodorin-thrombin crystal structure, a key to the TAP enigma? EMBO J 15: 6011-6017.
45. Macedo-Ribeiro S, Almeida C, Calisto BM, Friedrich T, Mentele R, et al. (2008) Isolation, cloning and structural characterisation of boophilin, a multifunctional Kunitz-type proteinase inhibitor from the cattle tick. PLoS ONE 3: e1624.
46. Bah A, Chen Z, Bush-Pelc LA, Mathews FS, Di Cera E, (2007) Crystal structures of murine thrombin in complex with the extracellular fragments of murine protease-activated receptors PAR3 and PAR4. Proc Natl Acad Sci U S A 104: 11603-11608.
47. Gandhi PS, Chen Z, Mathews FS, Di Cera E, (2008) Structural identification of the pathway of long-range communication in an allosteric enzyme. Proc Natl Acad Sci U S A 105: 1832-1837.
48. Martin PD, Robertson W, Turk D, Huber R, Bode W, et al. (1992) The structure of residues 7-16 of the A alpha-chain of human fibrinogen bound to bovine thrombin at 2.3-A resolution. J Biol Chem 267: 7911-7920.
49. Martin PD, Malkowski MG, DiMaio J, Konishi Y, Ni F, et al. (1996) Bovine thrombin complexed with an uncleavable analog of residues 7-19 of fibrinogen A alpha: geometry of the catalytic triad and interactions of the P1′, P2′, and P3′ substrate residues. Biochemistry 35: 13030-13039.
50. Stubbs MT, Oschkinat H, Mayr I, Huber R, Angliker H, et al. (1992) The interaction of thrombin with fibrinogen. A structural basis for its specificity. Eur J Biochem 206: 187-195.
51. Gandhi PS, Chen Z, Di Cera E, (2010) Crystal structure of thrombin bound to the uncleaved extracellular fragment of PAR1. J Biol Chem 285: 15393-15398.
52. Witting JI, Bourdon P, Brezniak DV, Maraganore JM, Fenton JW, (1992) Thrombin-specific inhibition by and slow cleavage of hirulog-1. Biochem J 283 (Pt 3): 737-743.
53. Matthews JH, Krishnan R, Costanzo MJ, Maryanoff BE, Tulinsky A, (1996) Crystal structures of thrombin with thiazole-containing inhibitors: probes of the S1′ binding site. Biophys J 71: 2830-2839.
54. Slon-Usakiewicz JJ, Sivaraman J, Li Y, Cygler M, Konishi Y, (2000) Design of P1′ and P3′ residues of trivalent thrombin inhibitors and their crystal structures. Biochemistry 39: 2384-2391.
55. Maraganore JM, Bourdon P, Jablonski J, Ramachandran KL, Fenton JW, (1990) Design and characterization of hirulogs: a novel class of bivalent peptide inhibitors of thrombin. Biochemistry 29: 7095-7101.
56. Fareed J, Jeske WP, (2004) Small-molecule direct antithrombins: argatroban. Best Pract Res Clin Haematol 17: 127-138.
57. Wienen W, Stassen JM, Priepke H, Ries UJ, Hauel N, (2007) In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Thromb Haemost 98: 155-162.
58. White CM, (2005) Thrombin-directed inhibitors: pharmacology and clinical use. Am Heart J 149: S54-S60.