1A46

THROMBIN COMPLEXED WITH HIRUGEN AND A BETA-STRAND MIMETIC INHIBITOR

1A46 の概要

• エントリーDOI: 10.2210/pdb1a46/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000617
• 分子名称: ALPHA-THROMBIN (SMALL SUBUNIT), ALPHA-THROMBIN (LARGE SUBUNIT), HIRUGEN, ... (6 entities in total)
• 機能のキーワード: complex (serine protease-inhibitor), 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 P09945; Secreted: P00734
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 35985.97

構造登録者

St Charles, R.,Matthews, J.H.,Zhang, E.,Tulinsky, A.,Kahn, M. (登録日: 1998-02-11, 公開日: 1998-05-27, 最終更新日: 2024-11-13)

主引用文献

St Charles, R.,Matthews, J.H.,Zhang, E.,Tulinsky, A.
Bound structures of novel P3-P1' beta-strand mimetic inhibitors of thrombin.
J.Med.Chem., 42:1376-1383, 1999

PubMed Abstract: The X-ray crystal structures of four beta-strand-templated active site inhibitors of thrombin containing P1' groups have been determined and refined at about 2.1-A resolution to crystallographic R-values between 0.148 and 0.164. Two of the inhibitors have an alpha-ketoamide functionality at the scissile bond; the other two have a nonhydrolyzable electrophilic group at the P1' position. The binding of lysine is compared with that of arginine at the S1 specificity site, while that of D,L-phenylalanine enantiomorphs is compared in the S3 region of thrombin. Four different P1' moieties bind at the S1' subsite in three different ways. The binding constants vary between 2.0 microM and 70 pM. The bound structures are used to intercorrelate the various binding constants and also lead to insightful inferences concerning binding at the S1' site of thrombin.

PubMed: 10212123
DOI: 10.1021/jm980052n

実験手法

X-RAY DIFFRACTION (2.12 Å)