1NFY

CRYSTAL STRUCTURE OF HUMAN COAGULATION FACTOR XA COMPLEXED WITH RPR200095

1NFY の概要

• エントリーDOI: 10.2210/pdb1nfy/pdb
• 関連するPDBエントリー: 1EZQ 1F0R 1F0S 1NFU 1NFW 1NFX
• 分子名称: Coagulation factor XA, heavy chain, Coagulation factor XA, light chain, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: 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: 44264.44

構造登録者

Maignan, S.,Guilloteau, J.P. (登録日: 2002-12-16, 公開日: 2003-02-25, 最終更新日: 2024-10-09)

主引用文献

Maignan, S.,Guilloteau, J.P.,Choi-Sledeski, Y.M.,Becker, M.R.,Ewing, W.R.,Pauls, H.W.,Spada, A.P.,Mikol, V.
Molecular structures of human Factor Xa complexed with ketopiperazine inhibitors: preference for a neutral group in the S1 pocket.
J.Med.Chem., 46:685-690, 2003

PubMed Abstract: The structures of the noncovalent complex of human factor Xa (fXa) with four non-peptide inhibitors containing a central sulfonylpiperazinone scaffold have been determined to about 2.1 A resolution. Highly potent fXa inhibitors containing both neutral groups such as chlorobenzothiophene or chlorothiophene and basic groups such as benzamidine were shown to interact in the S1 pocket through the neutral group whereas the S4 pocket is occupied by the basic moiety. The scaffold comprising the sulfonyl keto piperazine moiety might play a pivotal role in the orientation of substituents, since there is a strong hydrogen bond between Gly219 of fXa and the carbonyl oxygen of the piperazine. This unique "reverse" binding mode is heretofore unreported in fXa and shows that electrostatic interactions in the S1 subsite are not an absolute requirement to maintain high affinity. Selectivity against other serine proteases can be readily explained in light of these structural results. It has opened up new prospects for designing fXa inhibitors with increased oral bioavailability.

PubMed: 12593649
DOI: 10.1021/jm0203837

実験手法

X-RAY DIFFRACTION (2.1 Å)