1BMM

HUMAN ALPHA-THROMBIN COMPLEXED WITH [S-(R*,R*)]-4-[(AMINOIMINOMETHYL)AMINO]-N-[[1-[3-HYDROXY-2-[(2-NAPHTHALENYLSULFONYL)AMINO]-1-OXOPROPYL]-2-PYRROLIDINYL] METHYL]BUTANAMIDE (BMS-186282)

1BMM の概要

• エントリーDOI: 10.2210/pdb1bmm/pdb
• 分子名称: ALPHA-THROMBIN, HIRUDIN I, S-(R*,R*)]-4-[AMINOIMINOMETHYL)AMINO]-N-[[1-[3-HYDROXY -2-[(2-NAPHTHALENYLSULFONYL)AMINO]-1-OXOPROPYL]-2-PYRROLIDINYL] METHYL]BUTANAMIDE, ... (5 entities in total)
• 機能のキーワード: serine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space: P00734 P00734; Secreted: P28507
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 35849.87

構造登録者

Malley, M.,Sack, J. (登録日: 1995-11-14, 公開日: 1996-12-07, 最終更新日: 2011-07-13)

主引用文献

Malley, M.F.,Tabernero, L.,Chang, C.Y.,Ohringer, S.L.,Roberts, D.G.,Das, J.,Sack, J.S.
Crystallographic determination of the structures of human alpha-thrombin complexed with BMS-186282 and BMS-189090.
Protein Sci., 5:221-228, 1996

PubMed Abstract: The crystallographic structures of the ternary complexes of human alpha-thrombin with hirugen (a sulfated hirudin fragment) and the small-molecule active site thrombin inhibitors BMS-186282 and BMS-189090 have been determined at 2.6 and 2.8 A. In both cases, the inhibitors, which adopt very similar bound conformations, bind in an antiparallel beta-strand arrangement relative to the thrombin main chain in a manner like that reported for PPACK, D-Phe-Pro-Arg-CH2Cl. They do, however, exhibit differences in the binding of the alkyl guanidine moiety in the specificity pocket. Numerous hydrophilic and hydrophobic interactions serve to stabilize the inhibitors in the binding pocket. Although PPACK forms covalent bonds to both serine and the histidine of the catalytic triad of thrombin, neither BMS-186282 nor BMS-189090 bind covalently and only BMS-186282 forms a hydrogen bond to the serine of the catalytic triad. Both inhibitors bind with high affinity (Ki = 79 nM and 3.6 nM, respectively) and are highly selective for thrombin over trypsin and other serine proteases.

PubMed: 8745399

実験手法

X-RAY DIFFRACTION (2.6 Å)