4Y79

Factor Xa complex with GTC000406

4Y79 の概要

• エントリーDOI: 10.2210/pdb4y79/pdb
• 分子名称: Coagulation factor X, CALCIUM ION, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: hydrolase, inhibitor
• 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: 44267.70

構造登録者

Convery, M.A.,Young, R.J.,Senger, S.,Hamblin, J.N.,Chan, C.,Toomey, J.R.,Watson, N.S. (登録日: 2015-02-13, 公開日: 2015-09-30, 最終更新日: 2024-11-06)

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., 50:1546-1557, 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)