2J94

CRYSTAL STRUCTURE OF A HUMAN FACTOR XA INHIBITOR COMPLEX

2J94 の概要

• エントリーDOI: 10.2210/pdb2j94/pdb
• 関連するPDBエントリー: 1C5M 1EZQ 1F0R 1F0S 1FAX 1FJS 1FXY 1G2L 1G2M 1HCG 1IOE 1IQE 1IQF 1IQG 1IQH 1IQI 1IQJ 1IQK 1IQL 1IQM 1IQN 1KSN 1KYE 1LPG 1LPK 1LPZ 1LQD 1MQ5 1MQ6 1MSX 1NFU 1NFW 1NFX 1NFY 1NL8 1P0S 1V3X 1WU1 1XKA 1XKB 1Z6E 2BMG 2BOH 2BOK 2BQ6 2BQ7 2BQW 2CJI 2FZZ 2G00 2GD4 2J2U 2J34 2J38 2J4I 2J95
• 分子名称: COAGULATION FACTOR X, 5-(5-CHLORO-2-THIENYL)-N-{(3S)-1-[(1S)-1-METHYL-2-MORPHOLIN-4-YL-2-OXOETHYL]-2-OXOPYRROLIDIN-3-YL}-1H-1,2,4-TRIAZOLE-3-SULFONAMIDE, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: gamma- carboxyglutamic acid, serine protease, egf-like domain, blood coagulation, polymorphism, glycoprotein, hydroxylation, gamma-carboxyglutamic acid, calcium, zymogen, complex, protease, hydrolase
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Secreted: P00742 P00742
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44290.44

構造登録者

Chan, C.,Borthwick, A.D.,Brown, D.,Campbell, M.,Chaudry, L.,Chung, C.W.,Convery, M.A.,Hamblin, J.N.,Johnstone, L.,Kelly, H.A.,Kleanthous, S.,Burns-Kurtis, C.L.,Patikis, A.,Patel, C.,Pateman, A.J.,Senger, S.,Shah, G.P.,Toomey, J.R.,Watson, N.S.,Weston, H.E.,Whitworth, C.,Young, R.J.,Zhou, P. (登録日: 2006-11-02, 公開日: 2007-03-20, 最終更新日: 2024-11-13)

主引用文献

Chan, C.,Borthwick, A.D.,Brown, D.,Burns-Kurtis, C.L.,Campbell, M.,Chaudry, L.,Chung, C.W.,Convery, M.A.,Hamblin, J.N.,Johnstone, L.,Kelly, H.A.,Kleanthous, S.,Patikis, A.,Patel, C.,Pateman, A.J.,Senger, S.,Shah, G.P.,Toomey, J.R.,Watson, N.S.,Weston, H.E.,Whitworth, C.,Young, R.J.,Zhou, P.
Factor Xa Inhibitors: S1 Binding Interactions of a Series of N-{(3S)-1-[(1S)-1-Methyl-2-Morpholin-4-Yl-2-Oxoethyl]-2-Oxopyrrolidin-3-Yl}Sulfonamides.
J.Med.Chem., 50:1546-, 2007

PubMed Abstract: Factor Xa inhibitory activities for a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides with different P1 groups are described. These data provide insight into binding interactions within the S1 primary specificity pocket; rationales are presented for the derived SAR on the basis of electronic interactions through crystal structures of fXa-ligand complexes and molecular modeling studies. A good correlation between in vitro anticoagulant activities with lipophilicity and the extent of human serum albumin binding is observed within this series of potent fXa inhibitors. Pharmacokinetic profiles in rat and dog, together with selectivity over other trypsin-like serine proteases, identified 1f as a candidate for further evaluation.

PubMed: 17338508
DOI: 10.1021/JM060870C

実験手法

X-RAY DIFFRACTION (2.1 Å)