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. 1992 Apr;1(4):426–471. doi: 10.1002/pro.5560010402

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.

W Bode 1, D Turk 1, A Karshikov 1
PMCID: PMC2142221  PMID: 1304349

Abstract

Thrombin is a multifunctional serine proteinase that plays a key role in coagulation while exhibiting several other key cellular bioregulatory functions. The X-ray crystal structure of human alpha-thrombin was determined in its complex with the specific thrombin inhibitor D-Phe-Pro-Arg chloromethylketone (PPACK) using Patterson search methods and a search model derived from trypsinlike proteinases of known spatial structure (Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S.R., & Hofsteenge, J., 1989, EMBO J. 8, 3467-3475). The crystallographic refinement of the PPACK-thrombin model has now been completed at an R value of 0.156 (8 to 1.92 A); in particular, the amino- and the carboxy-termini of the thrombin A-chain are now defined and all side-chain atoms localized; only proline 37 was found to be in a cis-peptidyl conformation. The thrombin B-chain exhibits the characteristic polypeptide fold of trypsinlike serine proteinases; 195 residues occupy topologically equivalent positions with residues in bovine trypsin and 190 with those in bovine chymotrypsin with a root-mean-square (r.m.s.) deviation of 0.8 A for their alpha-carbon atoms. Most of the inserted residues constitute novel surface loops. A chymotrypsinogen numbering is suggested for thrombin based on the topological equivalences. The thrombin A-chain is arranged in a boomeranglike shape against the B-chain globule opposite to the active site; it resembles somewhat the propeptide of chymotrypsin(ogen) and is similarly not involved in substrate and inhibitor binding. Thrombin possesses an exceptionally large proportion of charged residues. The negatively and positively charged residues are not distributed uniformly over the whole molecule, but are clustered to form a sandwichlike electrostatic potential; in particular, two extended patches of mainly positively charged residues occur close to the carboxy-terminal B-chain helix (forming the presumed heparin-binding site) and on the surface of loop segment 70-80 (the fibrin[ogen] secondary binding exosite), respectively; the negatively charged residues are more clustered in the ringlike region between both poles, particularly around the active site. Several of the charged residues are involved in salt bridges; most are on the surface, but 10 charged protein groups form completely buried salt bridges and clusters. These electrostatic interactions play a particularly important role in the intrachain stabilization of the A-chain, in the coherence between the A- and the B-chain, and in the surface structure of the fibrin(ogen) secondary binding exosite (loop segment 67-80).(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Ascenzi P., Coletta M., Amiconi G., de Cristofaro R., Bolognesi M., Guarneri M., Menegatti E. Binding of the bovine basic pancreatic trypsin inhibitor (Kunitz) to human alpha-, beta- and gamma-thrombin; a kinetic and thermodynamic study. Biochim Biophys Acta. 1988 Sep 21;956(2):156–161. doi: 10.1016/0167-4838(88)90262-2. [DOI] [PubMed] [Google Scholar]
  2. Bajusz S., Barabás E., Tolnay P., Széll E., Bagdy D. Inhibition of thrombin and trypsin by tripeptide aldehydes. Int J Pept Protein Res. 1978 Oct;12(4):217–221. doi: 10.1111/j.1399-3011.1978.tb02889.x. [DOI] [PubMed] [Google Scholar]
  3. Bar-Shavit R., Eldor A., Vlodavsky I. Binding of thrombin to subendothelial extracellular matrix. Protection and expression of functional properties. J Clin Invest. 1989 Oct;84(4):1096–1104. doi: 10.1172/JCI114272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bar-Shavit R., Kahn A. J., Mann K. G., Wilner G. D. Growth-promoting effects of esterolytically inactive thrombin on macrophages. J Cell Biochem. 1986;32(4):261–272. doi: 10.1002/jcb.240320403. [DOI] [PubMed] [Google Scholar]
  5. Bar-Shavit R., Kahn A., Mudd M. S., Wilner G. D., Mann K. G., Fenton J. W., 2nd Localization of a chemotactic domain in human thrombin. Biochemistry. 1984 Jan 31;23(3):397–400. doi: 10.1021/bi00298a001. [DOI] [PubMed] [Google Scholar]
  6. Bar-Shavit R., Kahn A., Wilner G. D., Fenton J. W., 2nd Monocyte chemotaxis: stimulation by specific exosite region in thrombin. Science. 1983 May 13;220(4598):728–731. doi: 10.1126/science.6836310. [DOI] [PubMed] [Google Scholar]
  7. Bar-Shavit R., Sabbah V., Lampugnani M. G., Marchisio P. C., Fenton J. W., 2nd, Vlodavsky I., Dejana E. An Arg-Gly-Asp sequence within thrombin promotes endothelial cell adhesion. J Cell Biol. 1991 Jan;112(2):335–344. doi: 10.1083/jcb.112.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Baumann U., Huber R., Bode W., Grosse D., Lesjak M., Laurell C. B. Crystal structure of cleaved human alpha 1-antichymotrypsin at 2.7 A resolution and its comparison with other serpins. J Mol Biol. 1991 Apr 5;218(3):595–606. doi: 10.1016/0022-2836(91)90704-a. [DOI] [PubMed] [Google Scholar]
  9. Berg W., Hillvärn B., Arwin H., Stenberg M., Lundström I. The isoelectric point of thrombin and its behaviour compared to prothrombin at some solid surfaces. Thromb Haemost. 1979 Oct 31;42(3):972–982. [PubMed] [Google Scholar]
  10. Berliner L. J., Birktoft J. J., Miller T. L., Musci G., Scheffler J. E., Shen Y. Y., Sugawara Y. Thrombin: active-site topography. Ann N Y Acad Sci. 1986;485:80–95. doi: 10.1111/j.1749-6632.1986.tb34570.x. [DOI] [PubMed] [Google Scholar]
  11. Berliner L. J., Shen Y. Y. Physical evidence for an apolar binding site near the catalytic center of human alpha-thrombin. Biochemistry. 1977 Oct 18;16(21):4622–4626. doi: 10.1021/bi00640a015. [DOI] [PubMed] [Google Scholar]
  12. Berliner L. J., Sugawara Y., Fenton J. W., 2nd Human alpha-thrombin binding to nonpolymerized fibrin-Sepharose: evidence for an anionic binding region. Biochemistry. 1985 Nov 19;24(24):7005–7009. doi: 10.1021/bi00345a038. [DOI] [PubMed] [Google Scholar]
  13. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  14. Bezeaud A., Guillin M. C. Enzymic and nonenzymic properties of human beta-thrombin. J Biol Chem. 1988 Mar 15;263(8):3576–3581. [PubMed] [Google Scholar]
  15. Bing D. H., Cory M., Fenton J. W., 2nd Exo-site affinity labeling of human thrombins. Similar labeling on the A chain and B chain/fragments of clotting alpha- and nonclotting gamma/beta-thrombins. J Biol Chem. 1977 Nov 25;252(22):8027–8034. [PubMed] [Google Scholar]
  16. Bing D. H., Feldmann R. J., Fenton J. W., 2nd Structure-function relationships of thrombin based on the computer-generated three-dimensional model of the B chain of bovine thrombin. Ann N Y Acad Sci. 1986;485:104–119. doi: 10.1111/j.1749-6632.1986.tb34572.x. [DOI] [PubMed] [Google Scholar]
  17. Bizios R., Lai L., Fenton J. W., 2nd, Malik A. B. Thrombin-induced chemotaxis and aggregation of neutrophils. J Cell Physiol. 1986 Sep;128(3):485–490. doi: 10.1002/jcp.1041280318. [DOI] [PubMed] [Google Scholar]
  18. Björk I., Lindahl U. Mechanism of the anticoagulant action of heparin. Mol Cell Biochem. 1982 Oct 29;48(3):161–182. doi: 10.1007/BF00421226. [DOI] [PubMed] [Google Scholar]
  19. Blevins R. A., Tulinsky A. The refinement and the structure of the dimer of alpha-chymotrypsin at 1.67-A resolution. J Biol Chem. 1985 Apr 10;260(7):4264–4275. doi: 10.2210/pdb5cha/pdb. [DOI] [PubMed] [Google Scholar]
  20. Blombäck B., Blombäck M., Hessel B., Iwanaga S. Structure of N-terminal fragments of fibrinogen and specificity of thrombin. Nature. 1967 Sep 30;215(5109):1445–1448. doi: 10.1038/2151445a0. [DOI] [PubMed] [Google Scholar]
  21. Bode W., Chen Z., Bartels K., Kutzbach C., Schmidt-Kastner G., Bartunik H. Refined 2 A X-ray crystal structure of porcine pancreatic kallikrein A, a specific trypsin-like serine proteinase. Crystallization, structure determination, crystallographic refinement, structure and its comparison with bovine trypsin. J Mol Biol. 1983 Feb 25;164(2):237–282. doi: 10.1016/0022-2836(83)90077-3. [DOI] [PubMed] [Google Scholar]
  22. Bode W., Greyling H. J., Huber R., Otlewski J., Wilusz T. The refined 2.0 A X-ray crystal structure of the complex formed between bovine beta-trypsin and CMTI-I, a trypsin inhibitor from squash seeds (Cucurbita maxima). Topological similarity of the squash seed inhibitors with the carboxypeptidase A inhibitor from potatoes. FEBS Lett. 1989 Jan 2;242(2):285–292. doi: 10.1016/0014-5793(89)80486-7. [DOI] [PubMed] [Google Scholar]
  23. Bode W., Mayr I., Baumann U., Huber R., Stone S. R., Hofsteenge J. 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. 1989 Nov;8(11):3467–3475. doi: 10.1002/j.1460-2075.1989.tb08511.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Bode W., Papamokos E., Musil D. The high-resolution X-ray crystal structure of the complex formed between subtilisin Carlsberg and eglin c, an elastase inhibitor from the leech Hirudo medicinalis. Structural analysis, subtilisin structure and interface geometry. Eur J Biochem. 1987 Aug 3;166(3):673–692. doi: 10.1111/j.1432-1033.1987.tb13566.x. [DOI] [PubMed] [Google Scholar]
  25. Bode W., Schwager P., Huber R. The transition of bovine trypsinogen to a trypsin-like state upon strong ligand binding. The refined crystal structures of the bovine trypsinogen-pancreatic trypsin inhibitor complex and of its ternary complex with Ile-Val at 1.9 A resolution. J Mol Biol. 1978 Jan 5;118(1):99–112. doi: 10.1016/0022-2836(78)90246-2. [DOI] [PubMed] [Google Scholar]
  26. Bode W., Schwager P. The single calcium-binding site of crystallin bovin beta-trypsin. FEBS Lett. 1975 Aug 1;56(1):139–143. doi: 10.1016/0014-5793(75)80128-1. [DOI] [PubMed] [Google Scholar]
  27. Bode W., Turk D., Stürzebecher J. Geometry of binding of the benzamidine- and arginine-based inhibitors N alpha-(2-naphthyl-sulphonyl-glycyl)-DL-p-amidinophenylalanyl-pipe ridine (NAPAP) and (2R,4R)-4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulphonyl)-L-arginyl]-2-piperidine carboxylic acid (MQPA) to human alpha-thrombin. X-ray crystallographic determination of the NAPAP-trypsin complex and modeling of NAPAP-thrombin and MQPA-thrombin. Eur J Biochem. 1990 Oct 5;193(1):175–182. doi: 10.1111/j.1432-1033.1990.tb19320.x. [DOI] [PubMed] [Google Scholar]
  28. Bode W., Wei A. Z., Huber R., Meyer E., Travis J., Neumann S. X-ray crystal structure of the complex of human leukocyte elastase (PMN elastase) and the third domain of the turkey ovomucoid inhibitor. EMBO J. 1986 Oct;5(10):2453–2458. doi: 10.1002/j.1460-2075.1986.tb04521.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Boissel J. P., Le Bonniec B., Rabiet M. J., Labie D., Elion J. Covalent structures of beta and gamma autolytic derivatives of human alpha-thrombin. J Biol Chem. 1984 May 10;259(9):5691–5697. [PubMed] [Google Scholar]
  30. Braun P. J., Hofsteenge J., Chang J. Y., Stone S. R. Preparation and characterization of proteolyzed forms of human alpha-thrombin. Thromb Res. 1988 Apr 15;50(2):273–283. doi: 10.1016/0049-3848(88)90228-9. [DOI] [PubMed] [Google Scholar]
  31. Brezniak D. V., Brower M. S., Witting J. I., Walz D. A., Fenton J. W., 2nd Human alpha- to zeta-thrombin cleavage occurs with neutrophil cathepsin G or chymotrypsin while fibrinogen clotting activity is retained. Biochemistry. 1990 Apr 10;29(14):3536–3542. doi: 10.1021/bi00466a017. [DOI] [PubMed] [Google Scholar]
  32. Brower M. S., Walz D. A., Garry K. E., Fenton J. W., 2nd Human neutrophil elastase alters human alpha-thrombin function: limited proteolysis near the gamma-cleavage site results in decreased fibrinogen clotting and platelet-stimulatory activity. Blood. 1987 Mar;69(3):813–819. [PubMed] [Google Scholar]
  33. Brünger A. T., Kuriyan J., Karplus M. Crystallographic R factor refinement by molecular dynamics. Science. 1987 Jan 23;235(4787):458–460. doi: 10.1126/science.235.4787.458. [DOI] [PubMed] [Google Scholar]
  34. Burley S. K., Petsko G. A. Aromatic-aromatic interaction: a mechanism of protein structure stabilization. Science. 1985 Jul 5;229(4708):23–28. doi: 10.1126/science.3892686. [DOI] [PubMed] [Google Scholar]
  35. Butkowski R. J., Elion J., Downing M. R., Mann K. G. Primary structure of human prethrombin 2 and alpha-thrombin. J Biol Chem. 1977 Jul 25;252(14):4942–4957. [PubMed] [Google Scholar]
  36. Cardin A. D., Weintraub H. J. Molecular modeling of protein-glycosaminoglycan interactions. Arteriosclerosis. 1989 Jan-Feb;9(1):21–32. doi: 10.1161/01.atv.9.1.21. [DOI] [PubMed] [Google Scholar]
  37. Carney D. H., Herbosa G. J., Stiernberg J., Bergmann J. S., Gordon E. A., Scott D., Fenton J. W., 2nd Double-signal hypothesis for thrombin initiation of cell proliferation. Semin Thromb Hemost. 1986 Jul;12(3):231–240. doi: 10.1055/s-2007-1003559. [DOI] [PubMed] [Google Scholar]
  38. Chang J. Y. The hirudin-binding site of human alpha-thrombin. Identification of lysyl residues which participate in the combining site of hirudin-thrombin complex. J Biol Chem. 1989 May 5;264(13):7141–7146. [PubMed] [Google Scholar]
  39. Chang J. Y. The structures and proteolytic specificities of autolysed human thrombin. Biochem J. 1986 Dec 15;240(3):797–802. doi: 10.1042/bj2400797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Chang T., Feinman R. D., Landis B. H., Fenton J. W., 2nd Antithrombin reactions with alpha- and gamma-thrombins. Biochemistry. 1979 Jan 9;18(1):113–119. doi: 10.1021/bi00568a018. [DOI] [PubMed] [Google Scholar]
  41. Charo I. F., Bekeart L. S., Phillips D. R. Platelet glycoprotein IIb-IIIa-like proteins mediate endothelial cell attachment to adhesive proteins and the extracellular matrix. J Biol Chem. 1987 Jul 25;262(21):9935–9938. [PubMed] [Google Scholar]
  42. Church F. C., Pratt C. W., Noyes C. M., Kalayanamit T., Sherrill G. B., Tobin R. B., Meade J. B. Structural and functional properties of human alpha-thrombin, phosphopyridoxylated alpha-thrombin, and gamma T-thrombin. Identification of lysyl residues in alpha-thrombin that are critical for heparin and fibrin(ogen) interactions. J Biol Chem. 1989 Nov 5;264(31):18419–18425. [PubMed] [Google Scholar]
  43. Cohen G. H., Silverton E. W., Davies D. R. Refined crystal structure of gamma-chymotrypsin at 1.9 A resolution. Comparison with other pancreatic serine proteases. J Mol Biol. 1981 Jun 5;148(4):449–479. doi: 10.1016/0022-2836(81)90186-8. [DOI] [PubMed] [Google Scholar]
  44. Cunningham D. D., Farrell D. H. Thrombin interactions with cultured fibroblasts: relationship to mitogenic stimulation. Ann N Y Acad Sci. 1986;485:240–248. doi: 10.1111/j.1749-6632.1986.tb34586.x. [DOI] [PubMed] [Google Scholar]
  45. De Cristofaro R., Di Cera E. Effect of protons on the amidase activity of human alpha-thrombin. Analysis in terms of a general linkage scheme. J Mol Biol. 1990 Dec 20;216(4):1077–1085. doi: 10.1016/s0022-2836(99)80021-7. [DOI] [PubMed] [Google Scholar]
  46. Degen S. J., MacGillivray R. T., Davie E. W. Characterization of the complementary deoxyribonucleic acid and gene coding for human prothrombin. Biochemistry. 1983 Apr 26;22(9):2087–2097. doi: 10.1021/bi00278a008. [DOI] [PubMed] [Google Scholar]
  47. Dihanich M., Monard D. cDNA sequence of rat prothrombin. Nucleic Acids Res. 1990 Jul 25;18(14):4251–4251. doi: 10.1093/nar/18.14.4251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Dodt J., Köhler S., Baici A. Interaction of site specific hirudin variants with alpha-thrombin. FEBS Lett. 1988 Feb 29;229(1):87–90. doi: 10.1016/0014-5793(88)80803-2. [DOI] [PubMed] [Google Scholar]
  49. Doyle M. F., Mann K. G. Multiple active forms of thrombin. IV. Relative activities of meizothrombins. J Biol Chem. 1990 Jun 25;265(18):10693–10701. [PubMed] [Google Scholar]
  50. Elion J., Boissel J. P., Le Bonniec B., Bezeaud A., Jandrot-Perrus M., Rabiet M. J., Guillin M. C. Proteolytic derivatives of thrombin. Ann N Y Acad Sci. 1986;485:16–26. doi: 10.1111/j.1749-6632.1986.tb34564.x. [DOI] [PubMed] [Google Scholar]
  51. Esmon N. L., Carroll R. C., Esmon C. T. Thrombomodulin blocks the ability of thrombin to activate platelets. J Biol Chem. 1983 Oct 25;258(20):12238–12242. [PubMed] [Google Scholar]
  52. Esmon N. L., Owen W. G., Esmon C. T. Isolation of a membrane-bound cofactor for thrombin-catalyzed activation of protein C. J Biol Chem. 1982 Jan 25;257(2):859–864. [PubMed] [Google Scholar]
  53. Fenton J. W., 2nd, Olson T. A., Zabinski M. P., Wilner G. D. Anion-binding exosite of human alpha-thrombin and fibrin(ogen) recognition. Biochemistry. 1988 Sep 6;27(18):7106–7112. doi: 10.1021/bi00418a066. [DOI] [PubMed] [Google Scholar]
  54. Fenton J. W., 2nd Regulation of thrombin generation and functions. Semin Thromb Hemost. 1988 Jul;14(3):234–240. doi: 10.1055/s-2007-1002783. [DOI] [PubMed] [Google Scholar]
  55. Fenton J. W., 2nd Thrombin. Ann N Y Acad Sci. 1986;485:5–15. doi: 10.1111/j.1749-6632.1986.tb34563.x. [DOI] [PubMed] [Google Scholar]
  56. Fenton J. W., 2nd, Witting J. I., Pouliott C., Fareed J. Thrombin anion-binding exosite interactions with heparin and various polyanions. Ann N Y Acad Sci. 1989;556:158–165. doi: 10.1111/j.1749-6632.1989.tb22499.x. [DOI] [PubMed] [Google Scholar]
  57. Folkers P. J., Clore G. M., Driscoll P. C., Dodt J., Köhler S., Gronenborn A. M. Solution structure of recombinant hirudin and the Lys-47----Glu mutant: a nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing study. Biochemistry. 1989 Mar 21;28(6):2601–2617. doi: 10.1021/bi00432a038. [DOI] [PubMed] [Google Scholar]
  58. Freer S. T., Kraut J., Robertus J. D., Wright H. T., Xuong N. H. Chymotrypsinogen: 2.5-angstrom crystal structure, comparison with alpha-chymotrypsin, and implications for zymogen activation. Biochemistry. 1970 Apr 28;9(9):1997–2009. doi: 10.1021/bi00811a022. [DOI] [PubMed] [Google Scholar]
  59. Gilson M. K., Rashin A., Fine R., Honig B. On the calculation of electrostatic interactions in proteins. J Mol Biol. 1985 Aug 5;184(3):503–516. doi: 10.1016/0022-2836(85)90297-9. [DOI] [PubMed] [Google Scholar]
  60. Glenn K. C., Frost G. H., Bergmann J. S., Carney D. H. Synthetic peptides bind to high-affinity thrombin receptors and modulate thrombin mitogenesis. Pept Res. 1988 Nov-Dec;1(2):65–73. [PubMed] [Google Scholar]
  61. Greer J. Comparative model-building of the mammalian serine proteases. J Mol Biol. 1981 Dec 25;153(4):1027–1042. doi: 10.1016/0022-2836(81)90465-4. [DOI] [PubMed] [Google Scholar]
  62. Griffith M. J. Kinetics of the heparin-enhanced antithrombin III/thrombin reaction. Evidence for a template model for the mechanism of action of heparin. J Biol Chem. 1982 Jul 10;257(13):7360–7365. [PubMed] [Google Scholar]
  63. Hageman T. C., Endres G. F., Scheraga H. A. Mechanism of action of thrombin on fibrinogen. On the role of the A chain of bovine thrombin in specificity and in differentiating between thrombin and trypsin. Arch Biochem Biophys. 1975 Nov;171(1):327–336. doi: 10.1016/0003-9861(75)90039-9. [DOI] [PubMed] [Google Scholar]
  64. Hageman T. C., Scheraga H. A. Mechanism of action of thrombin on fibrinogen. Reaction of the N-terminal CNBr fragment from the Aalpha chain of human fibrinogen with bovine thrombin. Arch Biochem Biophys. 1974 Oct;164(2):707–715. doi: 10.1016/0003-9861(74)90083-6. [DOI] [PubMed] [Google Scholar]
  65. Hartley B. S., Kauffman D. L. Corrections to the amino acid sequence of bovine chymotrypsinogen A. Biochem J. 1966 Oct;101(1):229–231. doi: 10.1042/bj1010229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Haruyama H., Wüthrich K. Conformation of recombinant desulfatohirudin in aqueous solution determined by nuclear magnetic resonance. Biochemistry. 1989 May 16;28(10):4301–4312. doi: 10.1021/bi00436a027. [DOI] [PubMed] [Google Scholar]
  67. Henriksen R. A., Mann K. G. Identification of the primary structural defect in the dysthrombin thrombin Quick I: substitution of cysteine for arginine-382. Biochemistry. 1988 Dec 27;27(26):9160–9165. doi: 10.1021/bi00426a013. [DOI] [PubMed] [Google Scholar]
  68. Henriksen R. A., Mann K. G. Substitution of valine for glycine-558 in the congenital dysthrombin thrombin Quick II alters primary substrate specificity. Biochemistry. 1989 Mar 7;28(5):2078–2082. doi: 10.1021/bi00431a017. [DOI] [PubMed] [Google Scholar]
  69. Heuck C. C., Schiele U., Horn D., Fronda D., Ritz E. The role of surface charge on the accelerating action of heparin on the antithrombin III-inhibited activity of alpha-thrombin. J Biol Chem. 1985 Apr 25;260(8):4598–4603. [PubMed] [Google Scholar]
  70. Hofsteenge J., Taguchi H., Stone S. R. Effect of thrombomodulin on the kinetics of the interaction of thrombin with substrates and inhibitors. Biochem J. 1986 Jul 1;237(1):243–251. doi: 10.1042/bj2370243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Hogg D. H., Blombäck B. The mechanism of the fibrinogen-thrombin reaction. Thromb Res. 1978 Jun;12(6):953–964. doi: 10.1016/0049-3848(78)90051-8. [DOI] [PubMed] [Google Scholar]
  72. Hogg P. J., Jackson C. M. Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: implications for heparin efficacy. Proc Natl Acad Sci U S A. 1989 May;86(10):3619–3623. doi: 10.1073/pnas.86.10.3619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Huber R., Carrell R. W. Implications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins. Biochemistry. 1989 Nov 14;28(23):8951–8966. doi: 10.1021/bi00449a001. [DOI] [PubMed] [Google Scholar]
  74. Huber R., Kukla D., Bode W., Schwager P., Bartels K., Deisenhofer J., Steigemann W. Structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitor. II. Crystallographic refinement at 1.9 A resolution. J Mol Biol. 1974 Oct 15;89(1):73–101. doi: 10.1016/0022-2836(74)90163-6. [DOI] [PubMed] [Google Scholar]
  75. Jackson C. M., Nemerson Y. Blood coagulation. Annu Rev Biochem. 1980;49:765–811. doi: 10.1146/annurev.bi.49.070180.004001. [DOI] [PubMed] [Google Scholar]
  76. Jakubowski H. V., Owen W. G. Macromolecular specificity determinants on thrombin for fibrinogen and thrombomodulin. J Biol Chem. 1989 Jul 5;264(19):11117–11121. [PubMed] [Google Scholar]
  77. Kabsch W., Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983 Dec;22(12):2577–2637. doi: 10.1002/bip.360221211. [DOI] [PubMed] [Google Scholar]
  78. Kaczmarek E., McDonagh J. Thrombin binding to the A alpha-, B beta-, and gamma-chains of fibrinogen and to their remnants contained in fragment E. J Biol Chem. 1988 Sep 25;263(27):13896–13900. [PubMed] [Google Scholar]
  79. Kam C. M., Fujikawa K., Powers J. C. Mechanism-based isocoumarin inhibitors for trypsin and blood coagulation serine proteases: new anticoagulants. Biochemistry. 1988 Apr 5;27(7):2547–2557. doi: 10.1021/bi00407a042. [DOI] [PubMed] [Google Scholar]
  80. Kaminski M., McDonagh J. Inhibited thrombins. Interactions with fibrinogen and fibrin. Biochem J. 1987 Mar 15;242(3):881–887. doi: 10.1042/bj2420881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Karpatkin S., Karpatkin M. Inhibition of the enzymatic activity of thrombin by concanavalin A. Biochem Biophys Res Commun. 1974 Apr 23;57(4):1111–1118. doi: 10.1016/0006-291x(74)90811-0. [DOI] [PubMed] [Google Scholar]
  82. Kawabata S., Morita T., Iwanaga S., Igarashi H. Staphylocoagulase-binding region in human prothrombin. J Biochem. 1985 Jan;97(1):325–331. doi: 10.1093/oxfordjournals.jbchem.a135057. [DOI] [PubMed] [Google Scholar]
  83. Kettner C., Shaw E. D-Phe-Pro-ArgCH2C1-A selective affinity label for thrombin. Thromb Res. 1979;14(6):969–973. doi: 10.1016/0049-3848(79)90014-8. [DOI] [PubMed] [Google Scholar]
  84. Klapper I., Hagstrom R., Fine R., Sharp K., Honig B. Focusing of electric fields in the active site of Cu-Zn superoxide dismutase: effects of ionic strength and amino-acid modification. Proteins. 1986 Sep;1(1):47–59. doi: 10.1002/prot.340010109. [DOI] [PubMed] [Google Scholar]
  85. Landis B. H., Koehler K. A., Fenton J. W., 2nd Human thrombins. Group IA and IIA salt-dependent properties of alpha-thrombin. J Biol Chem. 1981 May 10;256(9):4604–4610. [PubMed] [Google Scholar]
  86. Laskowski M., Jr, Kato I. Protein inhibitors of proteinases. Annu Rev Biochem. 1980;49:593–626. doi: 10.1146/annurev.bi.49.070180.003113. [DOI] [PubMed] [Google Scholar]
  87. Le Bonniec B. F., Esmon C. T. Glu-192----Gln substitution in thrombin mimics the catalytic switch induced by thrombomodulin. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7371–7375. doi: 10.1073/pnas.88.16.7371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Le Bonniec B. F., MacGillivray R. T., Esmon C. T. Thrombin Glu-39 restricts the P'3 specificity to nonacidic residues. J Biol Chem. 1991 Jul 25;266(21):13796–13803. [PubMed] [Google Scholar]
  89. Lee B., Richards F. M. The interpretation of protein structures: estimation of static accessibility. J Mol Biol. 1971 Feb 14;55(3):379–400. doi: 10.1016/0022-2836(71)90324-x. [DOI] [PubMed] [Google Scholar]
  90. Levitt M. Energy refinement of hen egg-white lysozyme. J Mol Biol. 1974 Jan 25;82(3):393–420. doi: 10.1016/0022-2836(74)90599-3. [DOI] [PubMed] [Google Scholar]
  91. Lewis S. D., Lorand L., Fenton J. W., 2nd, Shafer J. A. Catalytic competence of human alpha- and gamma-thrombin in the activation of fibrinogen and factor XIII. Biochemistry. 1987 Dec 1;26(24):7597–7603. doi: 10.1021/bi00398a010. [DOI] [PubMed] [Google Scholar]
  92. Liem R. K., Scheraga H. A. Mechanism of action of thrombin on fibrinogen. IV. Further mapping of the active sites of thrombin and trypsin. Arch Biochem Biophys. 1974 Jan;160(1):333–339. doi: 10.1016/s0003-9861(74)80041-x. [DOI] [PubMed] [Google Scholar]
  93. Liu C. Y., Nossel H. L., Kaplan K. L. The binding of thrombin by fibrin. J Biol Chem. 1979 Oct 25;254(20):10421–10425. [PubMed] [Google Scholar]
  94. Liu L. W., Vu T. K., Esmon C. T., Coughlin S. R. The region of the thrombin receptor resembling hirudin binds to thrombin and alters enzyme specificity. J Biol Chem. 1991 Sep 15;266(26):16977–16980. [PubMed] [Google Scholar]
  95. Loebermann H., Tokuoka R., Deisenhofer J., Huber R. Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function. J Mol Biol. 1984 Aug 15;177(3):531–557. [PubMed] [Google Scholar]
  96. Lundblad R. L., Noyes C. M., Featherstone G. L., Harrison J. H., Jenzano J. W. The reaction of bovine alpha-thrombin with tetranitromethane. Characterization of the modified protein. J Biol Chem. 1988 Mar 15;263(8):3729–3734. [PubMed] [Google Scholar]
  97. Maraganore J. M., Bourdon P., Jablonski J., Ramachandran K. L., Fenton J. W., 2nd Design and characterization of hirulogs: a novel class of bivalent peptide inhibitors of thrombin. Biochemistry. 1990 Jul 31;29(30):7095–7101. doi: 10.1021/bi00482a021. [DOI] [PubMed] [Google Scholar]
  98. Marsh H. C., Jr, Meinwald Y. C., Lee S., Martinelli R. A., Scheraga H. A. Mechanism of action of thrombin on fibrinogen: NMR evidence for a beta-bend at or near fibrinogen A alpha Gly(P5)-Gly(P4). Biochemistry. 1985 May 21;24(11):2806–2812. doi: 10.1021/bi00332a031. [DOI] [PubMed] [Google Scholar]
  99. Matthew J. B. Electrostatic effects in proteins. Annu Rev Biophys Biophys Chem. 1985;14:387–417. doi: 10.1146/annurev.bb.14.060185.002131. [DOI] [PubMed] [Google Scholar]
  100. McGowan E. B., Detwiler T. C. Modified platelet responses to thrombin. Evidence for two types of receptors or coupling mechanisms. J Biol Chem. 1986 Jan 15;261(2):739–746. [PubMed] [Google Scholar]
  101. Meinwald Y. C., Martinelli R. A., van Nispen J. W., Scheraga H. A. Mechanism of action of thrombin on fibrinogen. Size of the A alpha fibrinogen-like peptide that contacts the active site of thrombin. Biochemistry. 1980 Aug 5;19(16):3820–3825. doi: 10.1021/bi00557a026. [DOI] [PubMed] [Google Scholar]
  102. Meloun B., Kluh I., Kostka V., Morávek L., Prusík Z., Vanecek J., Keil B., Sorm F. Covalent structure of bovine chymotrypsinogen A. Biochim Biophys Acta. 1966 Dec 28;130(2):543–546. doi: 10.1016/0304-4165(66)90258-3. [DOI] [PubMed] [Google Scholar]
  103. Meyer E., Cole G., Radhakrishnan R., Epp O. Structure of native porcine pancreatic elastase at 1.65 A resolutions. Acta Crystallogr B. 1988 Feb 1;44(Pt 1):26–38. doi: 10.1107/s0108768187007559. [DOI] [PubMed] [Google Scholar]
  104. Mikes O., Holeysovský V., Tomásek V., Sorm F. Covalent structure of bovine trypsinogen. The position of the remaining amides. Biochem Biophys Res Commun. 1966 Aug 12;24(3):346–352. doi: 10.1016/0006-291x(66)90162-8. [DOI] [PubMed] [Google Scholar]
  105. Miyata T., Morita T., Inomoto T., Kawauchi S., Shirakami A., Iwanaga S. Prothrombin Tokushima, a replacement of arginine-418 by tryptophan that impairs the fibrinogen clotting activity of derived thrombin Tokushima. Biochemistry. 1987 Feb 24;26(4):1117–1122. doi: 10.1021/bi00378a020. [DOI] [PubMed] [Google Scholar]
  106. Naski M. C., Fenton J. W., 2nd, Maraganore J. M., Olson S. T., Shafer J. A. The COOH-terminal domain of hirudin. An exosite-directed competitive inhibitor of the action of alpha-thrombin on fibrinogen. J Biol Chem. 1990 Aug 15;265(23):13484–13489. [PubMed] [Google Scholar]
  107. Needleman S. B., Wunsch C. D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970 Mar;48(3):443–453. doi: 10.1016/0022-2836(70)90057-4. [DOI] [PubMed] [Google Scholar]
  108. Nesheim M. E. A simple rate law that describes the kinetics of the heparin-catalyzed reaction between antithrombin III and thrombin. J Biol Chem. 1983 Dec 10;258(23):14708–14717. [PubMed] [Google Scholar]
  109. Ni F., Konishi Y., Frazier R. B., Scheraga H. A., Lord S. T. High-resolution NMR studies of fibrinogen-like peptides in solution: interaction of thrombin with residues 1-23 of the A alpha chain of human fibrinogen. Biochemistry. 1989 Apr 4;28(7):3082–3094. doi: 10.1021/bi00433a052. [DOI] [PubMed] [Google Scholar]
  110. Ni F., Meinwald Y. C., Vásquez M., Scheraga H. A. High-resolution NMR studies of fibrinogen-like peptides in solution: structure of a thrombin-bound peptide corresponding to residues 7-16 of the A alpha chain of human fibrinogen. Biochemistry. 1989 Apr 4;28(7):3094–3105. doi: 10.1021/bi00433a053. [DOI] [PubMed] [Google Scholar]
  111. Nilsson B., Horne M. K., 3rd, Gralnick H. R. The carbohydrate of human thrombin: structural analysis of glycoprotein oligosaccharides by mass spectrometry. Arch Biochem Biophys. 1983 Jul 1;224(1):127–133. doi: 10.1016/0003-9861(83)90196-0. [DOI] [PubMed] [Google Scholar]
  112. Noé G., Hofsteenge J., Rovelli G., Stone S. R. The use of sequence-specific antibodies to identify a secondary binding site in thrombin. J Biol Chem. 1988 Aug 25;263(24):11729–11735. [PubMed] [Google Scholar]
  113. Okamoto S., Hijikata A., Kikumoto R., Tonomura S., Hara H., Ninomiya K., Maruyama A., Sugano M., Tamao Y. Potent inhibition of thrombin by the newly synthesized arginine derivative No. 805. The importance of stereo-structure of its hydrophobic carboxamide portion. Biochem Biophys Res Commun. 1981 Jul 30;101(2):440–446. doi: 10.1016/0006-291x(81)91279-1. [DOI] [PubMed] [Google Scholar]
  114. Olson S. T., Shore J. D. Demonstration of a two-step reaction mechanism for inhibition of alpha-thrombin by antithrombin III and identification of the step affected by heparin. J Biol Chem. 1982 Dec 25;257(24):14891–14895. [PubMed] [Google Scholar]
  115. Olson T. A., Sonder S. A., Wilner G. D., Fenton J. W., 2nd Heparin binding in proximity to the catalytic site of human alpha-thrombin. Ann N Y Acad Sci. 1986;485:96–103. doi: 10.1111/j.1749-6632.1986.tb34571.x. [DOI] [PubMed] [Google Scholar]
  116. Patthy L. Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules. Cell. 1985 Jul;41(3):657–663. doi: 10.1016/s0092-8674(85)80046-5. [DOI] [PubMed] [Google Scholar]
  117. Pomerantz M. W., Owen W. G. A catalytic role for heparin. Evidence for a ternary complex of heparin cofactor thrombin and heparin. Biochim Biophys Acta. 1978 Jul 21;535(1):66–77. doi: 10.1016/0005-2795(78)90033-8. [DOI] [PubMed] [Google Scholar]
  118. Preissner K. T., Delvos U., Müller-Berghaus G. Binding of thrombin to thrombomodulin accelerates inhibition of the enzyme by antithrombin III. Evidence for a heparin-independent mechanism. Biochemistry. 1987 May 5;26(9):2521–2528. doi: 10.1021/bi00383a018. [DOI] [PubMed] [Google Scholar]
  119. Prescott S. M., Seeger A. R., Zimmerman G. A., McIntyre T. M., Maraganore J. M. Hirudin-based peptides block the inflammatory effects of thrombin on endothelial cells. J Biol Chem. 1990 Jun 15;265(17):9614–9616. [PubMed] [Google Scholar]
  120. Ramakrishnan C., Ramachandran G. N. Stereochemical criteria for polypeptide and protein chain conformations. II. Allowed conformations for a pair of peptide units. Biophys J. 1965 Nov;5(6):909–933. doi: 10.1016/S0006-3495(65)86759-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Remington S. J., Woodbury R. G., Reynolds R. A., Matthews B. W., Neurath H. The structure of rat mast cell protease II at 1.9-A resolution. Biochemistry. 1988 Oct 18;27(21):8097–8105. doi: 10.1021/bi00421a019. [DOI] [PubMed] [Google Scholar]
  122. Richards F. M. Areas, volumes, packing and protein structure. Annu Rev Biophys Bioeng. 1977;6:151–176. doi: 10.1146/annurev.bb.06.060177.001055. [DOI] [PubMed] [Google Scholar]
  123. Rosenberg R. D., Damus P. S. The purification and mechanism of action of human antithrombin-heparin cofactor. J Biol Chem. 1973 Sep 25;248(18):6490–6505. [PubMed] [Google Scholar]
  124. Rossmann M. G., Argos P. A comparison of the heme binding pocket in globins and cytochrome b5. J Biol Chem. 1975 Sep 25;250(18):7525–7532. [PubMed] [Google Scholar]
  125. Rydel T. J., Ravichandran K. G., Tulinsky A., Bode W., Huber R., Roitsch C., Fenton J. W., 2nd The structure of a complex of recombinant hirudin and human alpha-thrombin. Science. 1990 Jul 20;249(4966):277–280. doi: 10.1126/science.2374926. [DOI] [PubMed] [Google Scholar]
  126. Rydel T. J., Tulinsky A., Bode W., Huber R. Refined structure of the hirudin-thrombin complex. J Mol Biol. 1991 Sep 20;221(2):583–601. doi: 10.1016/0022-2836(91)80074-5. [DOI] [PubMed] [Google Scholar]
  127. Schechter I., Berger A. On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun. 1967 Apr 20;27(2):157–162. doi: 10.1016/s0006-291x(67)80055-x. [DOI] [PubMed] [Google Scholar]
  128. Schirmer T., Bode W., Huber R. Refined three-dimensional structures of two cyanobacterial C-phycocyanins at 2.1 and 2.5 A resolution. A common principle of phycobilin-protein interaction. J Mol Biol. 1987 Aug 5;196(3):677–695. doi: 10.1016/0022-2836(87)90040-4. [DOI] [PubMed] [Google Scholar]
  129. Shuman M. A. Thrombin-cellular interactions. Ann N Y Acad Sci. 1986;485:228–239. doi: 10.1111/j.1749-6632.1986.tb34585.x. [DOI] [PubMed] [Google Scholar]
  130. Skaug K., Christensen T. B. The significance of the carbohydrate constituents of bovine thrombin for the clotting activity. Biochim Biophys Acta. 1971;230(3):627–629. doi: 10.1016/0304-4165(71)90197-8. [DOI] [PubMed] [Google Scholar]
  131. Sonder S. A., Fenton J. W., 2nd Proflavin binding within the fibrinopeptide groove adjacent to the catalytic site of human alpha-thrombin. Biochemistry. 1984 Apr 10;23(8):1818–1823. doi: 10.1021/bi00303a037. [DOI] [PubMed] [Google Scholar]
  132. Stone S. R., Braun P. J., Hofsteenge J. Identification of regions of alpha-thrombin involved in its interaction with hirudin. Biochemistry. 1987 Jul 28;26(15):4617–4624. doi: 10.1021/bi00389a004. [DOI] [PubMed] [Google Scholar]
  133. Stone S. R., Hofsteenge J. Kinetics of the inhibition of thrombin by hirudin. Biochemistry. 1986 Aug 12;25(16):4622–4628. doi: 10.1021/bi00364a025. [DOI] [PubMed] [Google Scholar]
  134. Sugawara Y., Birktoft J. J., Berliner L. J. Human alpha- and gamma-thrombin inhibition by trypsin inhibitors supports predictions from molecular graphics experiments. Semin Thromb Hemost. 1986 Jul;12(3):209–212. doi: 10.1055/s-2007-1003552. [DOI] [PubMed] [Google Scholar]
  135. Suzuki K., Nishioka J., Hayashi T. Localization of thrombomodulin-binding site within human thrombin. J Biol Chem. 1990 Aug 5;265(22):13263–13267. [PubMed] [Google Scholar]
  136. Thomas K. A., Smith G. M., Thomas T. B., Feldmann R. J. Electronic distributions within protein phenylalanine aromatic rings are reflected by the three-dimensional oxygen atom environments. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4843–4847. doi: 10.1073/pnas.79.16.4843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  137. Thompson A. R. High affinity binding of human and bovine thrombins to p-chlorobenzylamido-epsilon-aminocaproyl agarose. Biochim Biophys Acta. 1976 Jan 23;422(1):200–209. doi: 10.1016/0005-2744(76)90019-x. [DOI] [PubMed] [Google Scholar]
  138. Tollefsen D. M., Majerus D. W., Blank M. K. Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma. J Biol Chem. 1982 Mar 10;257(5):2162–2169. [PubMed] [Google Scholar]
  139. Toma K., Suzuki K. Mapping active sites of blood coagulation serine proteases--activated protein C and thrombin--on simple graphics models. J Mol Graph. 1989 Sep;7(3):146-9, 154-5. doi: 10.1016/0263-7855(89)80018-9. [DOI] [PubMed] [Google Scholar]
  140. Tsiang M., Lentz S. R., Dittman W. A., Wen D., Scarpati E. M., Sadler J. E. Equilibrium binding of thrombin to recombinant human thrombomodulin: effect of hirudin, fibrinogen, factor Va, and peptide analogues. Biochemistry. 1990 Nov 27;29(47):10602–10612. doi: 10.1021/bi00499a005. [DOI] [PubMed] [Google Scholar]
  141. Tsukada H., Blow D. M. Structure of alpha-chymotrypsin refined at 1.68 A resolution. J Mol Biol. 1985 Aug 20;184(4):703–711. doi: 10.1016/0022-2836(85)90314-6. [DOI] [PubMed] [Google Scholar]
  142. Turk D., Stürzebecher J., Bode W. Geometry of binding of the N alpha-tosylated piperidides of m-amidino-, p-amidino- and p-guanidino phenylalanine to thrombin and trypsin. X-ray crystal structures of their trypsin complexes and modeling of their thrombin complexes. FEBS Lett. 1991 Aug 5;287(1-2):133–138. doi: 10.1016/0014-5793(91)80033-y. [DOI] [PubMed] [Google Scholar]
  143. Vu T. K., Hung D. T., Wheaton V. I., Coughlin S. R. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991 Mar 22;64(6):1057–1068. doi: 10.1016/0092-8674(91)90261-v. [DOI] [PubMed] [Google Scholar]
  144. WALSH K. A., NEURATH H. TRYPSINOGEN AND CHYMOTRYPSINOGEN AS HOMOLOGOUS PROTEINS. Proc Natl Acad Sci U S A. 1964 Oct;52:884–889. doi: 10.1073/pnas.52.4.884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  145. Wallace A., Rovelli G., Hofsteenge J., Stone S. R. Effect of heparin on the glia-derived-nexin-thrombin interaction. Biochem J. 1989 Jan 1;257(1):191–196. doi: 10.1042/bj2570191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  146. Wang D., Bode W., Huber R. Bovine chymotrypsinogen A X-ray crystal structure analysis and refinement of a new crystal form at 1.8 A resolution. J Mol Biol. 1985 Oct 5;185(3):595–624. doi: 10.1016/0022-2836(85)90074-9. [DOI] [PubMed] [Google Scholar]
  147. Wei A. Z., Mayr I., Bode W. The refined 2.3 A crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor. FEBS Lett. 1988 Jul 18;234(2):367–373. doi: 10.1016/0014-5793(88)80118-2. [DOI] [PubMed] [Google Scholar]
  148. White G. C., Lundblad R. L., Griffith M. J. Structure-function relations in platelet-thrombin reactions. Inhibition of platelet-thrombin interactions by lysine modification. J Biol Chem. 1981 Feb 25;256(4):1763–1766. [PubMed] [Google Scholar]
  149. van Nispen J. W., Hageman T. C., Scheraga H. A. Mechanism of action of thrombin on fibrinogen. The reaction of thrombin with fibrinogen-like peptides containing 11, 14, and 16 residues. Arch Biochem Biophys. 1977 Jul;182(1):227–243. doi: 10.1016/0003-9861(77)90303-4. [DOI] [PubMed] [Google Scholar]

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