The crystal structure of human α-thrombin complexed with LY178550, a nonpeptidyl, active site-directed inhibitor

Protein Science

Volumn 6, Issue 7, 1997, Pages 1412-1417

  Chirgadze, Nickolay Y ^a   Sall, Daniel J ^a   Klimkowski, Valentine J ^a   Clawson, David K ^a   Briggs, Steve L ^a   Hermann, Robert ^a   Smith, Gerald F ^a   Gifford Moore, Donetta S ^a   Wery, Jean Pierre ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

Crystallography; Human thrombin; Nonpeptidyl inhibitor; Structure based drug design

Indexed keywords

1 [[5 (AMINOIMINOMETHYL) 1H INDOL 2 YL]CARBONYL] 4 (PHENYLMETHYL)PIPERIDINE; ASPARTIC ACID; GLYCINE; PIPERIDINE DERIVATIVE; SERINE; THROMBIN; THROMBIN INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; COMPLEX FORMATION; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; HUMAN; PRIORITY JOURNAL; X RAY CRYSTALLOGRAPHY;

EID: 0030835791     PISSN: 09618368     EISSN: None     Source Type: Journal    
DOI: 10.1002/pro.5560060705     Document Type: Article

References (26)

1. Ajay, Murko MA. 1995. Computational methods to predict binding free energy in ligand-receptor complexes. J Med Chem 38:4953-4967.
2. Ashley JN, Barber HJ, Ewins AJ, Newberry G, Self ADHA. 1942. Chemotherapeutic comparison of the trypanocidal action of some aromatic diamidines. J Chem Soc:103-116.
3. Brünger AT. 1992. X-PLOR, version 3.1. A system for X-ray crystallography and NMR. New Haven, Connecticut: Yale University Press.
4. Chirgadze NY, Clawson DK, Gesellchen PD, Hermann RB, Kaiser RE, Olkowski JL, Sall DJ, Schevitz RW, Smith GF, Shuman RT, Wery JP, Jones ND. 1992. The X-ray structure at 2.2 Å of a ternary complex containing human α-thrombin, a hirudin peptide (54-65) and an active site inhibitor. American Cristallographic Association Meeting 20:116. [Abstr. PB311].
5. Engh RA, Huber R, 1991. Accurate bond and angle parameters for X-ray protein structure refinement. Acta Crystallogr A 47:392-400.
6. Geratz JD, Stevens FM, Polakoski KL, Parrish RF, Tidwell RR. 1979. Amidino-substituted aromatic heterocycles as probes of the specificity pocket of trypsin-like proteases. Arch Biochem Biophys 197:551-559.
7. Hartley BS, Shotton DM. 1971. Pancreatic elastase. In: Boyer PD, ed. The enzymes 3. New York/London: Academic Press. pp 323-373.
8. Iwanowicz EJ, Lau WF, Lin J, Roberts DGM, Seiler SM. 1996. Derivatives of 5-amidine indole as inhibitors of thrombin catalytic activity. Bioorg Medicinal Chem Letts 6:1339-1344.
9. Jones TA. 1978. A graphics model building and refinement system for macro-molecules. J Appl Crystallogr 11:268-272.
10. Lindwall HG, Mantell GJ. 1953. Synthesis and reactions of indole carboxylic acids: Pyridindolones from indole-2-carboxyacetalylbenzylamides. J Org Chem 18:345-357.
11. Luzzati PV. 1952. Traitement statistique des erreurs dans la determination des structures cristallines. Acta Crystallogr 5:802-810.
12. Machovich R. 1984. Thrombin and hemostasis. In: Machovich R, ed. The thrombin. Boca Raton, Florida: CRC Press Inc. pp 1-22.
13. Malley MF, Tabernero L, Chang CY, Ohringer SL, Roberts DGM, Das J, Sack JS. 1996. Crystallographic determination of the structures of human α-thrombin complexed with BMS-186282 and BMS-189090. Protein Sci 5:221-228.
14. McDonald IK, Thornton JM. 1994. Satisfying hydrogen bonding potential in proteins. J Mol Biol 238:777-793.
15. Minor W. 1993. XDSPLAYF Program. West Lafayette, Indiana: Purdue University.
16. Otwinowski Z. 1993. Oscillation data reduction program. In: Proceedings of the CCP4 study weekend: Data collection and processing. Warrington, UK: SERC Daresbury Laboratory. pp 56-62.
17. a. Annu Rep Med Chem 30:71-80.
18. Schacht AL, Chirgadze NY, Clawson DK, Craft TJ, Coffman WJ, Jones ND, Gifford-Moore DS, Olkowski J, Shuman RT, Smith GF, Weir LC, Wiley MR. 1995. N-substituted glycines as replacements for proline in tripeptide aldehyde thrombin inhibitors. Bioorg Med Chem Lett 5:2529-2534.
19. Sherry S, Alkjaersig N, Fletcher AP. 1965. Comparative activity of thrombin on substituted arginine and lysine esters. Am J Physiol 209:577-583.
20. Shibata A. 1990. Diffraction data collection with R-AXIS II, an X-ray detecting system using imaging plate. The Rigaku Journal 7:28-32.
21. Shuman RT, Rothenberger RB, Campbell CS, Smith GF, Gifford-Moore DS, Gesellchen PD. 1993. Highly selective tripeptide thrombin inhibitors. J Med Chem 36:314-319.
22. Skrzypczak-Janjun E, Carpenos V, Ravichandran KG, Tulinsky A, Westbrook M, Maraganore JM. 1991. The structure of hirugen and hirulog 1 complexes of α-thrombin. J Mol Biol 221:1379-1393.
23. Smith GF, Craft TJ, Gifford-Moore DS, Coffman WJ, Kurz KD, Roberts E, RT Shuman RT, Sandusky GE, Jones ND, Chirgadze NY, Jackson CV. 1996. A family of arginal thrombin inhibitors related to efegatran. Seminars in Thrombosis and Hemostasis 22:173-183.
24. Smith GF, Neubauer BL, Sundboom JL, Best KL, Goode RL, Tanzer LR, Merriman RL, Frank JD, Herrmann RG. 1988. Correlation of the in vivo anticoagulant, antithrombotic, and antimetastatic efficacy of warfarin in the rat. Thromb Res 50:163-174.
25. Tabernero L, Chang CY, Ohringer SL, Lau WF, Iwanowicz EJ, Han WC, Wang TC, Seiler SM, Roberts DSM, Sack JS. 1995. Structure of a retro-binding peptide inhibitor complexed with human α-thrombin. J Mol Biol 246:14-20.
26. Wallace AC, Laskowski RA, Thornton JM. 1995. LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8:127-134.