1NY2

Human alpha thrombin inhibited by RPPGF and hirugen

1NY2 の概要

• エントリーDOI: 10.2210/pdb1ny2/pdb
• 関連するPDBエントリー: 1HDT 1TMU 7KME 8KME
• 分子名称: thrombin light chain, thrombin Heavy chain, Hirugen, ... (5 entities in total)
• 機能のキーワード: thrombosis, retro binding, hydrolase, 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: P28504
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 35813.82

構造登録者

Krishnan, R.,Tulinsky, A.,Schmaier, A.H.,Hasan, A.A.,Warnock, M.,Srikanth, S.,Mahdi, F. (登録日: 2003-02-11, 公開日: 2003-03-04, 最終更新日: 2023-11-15)

主引用文献

Hasan, A.A.,Warnock, M.,Nieman, M.,Srikanth, S.,Mahdi, F.,Krishnan, R.,Tulinsky, A.,Schmaier, A.H.
Mechanisms of Arg-Pro-Pro-Gly-Phe inhibition of thrombin.
Am.J.Physiol.Heart Circ.Physiol., 285:H183-H193, 2003

PubMed Abstract: Investigations determined the mechanism(s) by which Arg-Pro-Pro-Gly-Phe (RPPGF) inhibits thrombin-induced platelet activation. High concentrations of RPPGF inhibit thrombin-induced coagulant activity. RPPGF binds to the active site of thrombin by forming a parallel beta-strand with Ser214-Gly216 and interacts with His57, Asp189, and Ser195 of the catalytic triad. RPPGF competitively inhibits alpha-thrombin from hydrolyzing Sar-Pro-Arg-paranitroanilide with a Ki = 1.75 +/- 0.03 mM. Other mechanisms were sought to explain why RPPGF inhibits thrombin activation of platelets at concentrations below that which inhibits its active site. Soluble RPPGF blocks biotinylated NATLDPRSFLLR of the thrombin cleavage site on protease-activated receptor (PAR)1 from binding to the peptide RPPGC (IC50 = 20 microM). The soluble recombinant extracellular domain of PAR1 (rPAR1EC) blocks biotinylated RPPGF binding to rPAR1EC (IC50 = 50 microM) bound to microtiter plates, but rPAR1EC deletion mutants missing the sequence LDPR or PRSF do not. RPPGF and related forms prevent the thrombin-like enzyme thrombocytin from proteolyzing rPAR1EC at concentrations that do not block thrombocytin's active site. These studies indicate that RPPGF is a bifunctional inhibitor of thrombin: it binds to PAR1 to prevent thrombin cleavage at Arg41 and interacts with the active site of alpha-thrombin.

PubMed: 12598231
DOI: 10.1152/ajpheart.00490.2002

実験手法

X-RAY DIFFRACTION (2.3 Å)