3JZ2

Crystal structure of human thrombin mutant N143P in E* form

3JZ2 の概要

• エントリーDOI: 10.2210/pdb3jz2/pdb
• 関連するPDBエントリー: 1SHH 3BEI 3JZ1
• 分子名称: Thrombin light chain, Thrombin heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: serine protease, acute phase, blood coagulation, cleavage on pair of basic residues, disease mutation, disulfide bond, gamma-carboxyglutamic acid, glycoprotein, hydrolase, kringle, protease, secreted, zymogen
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34449.35

構造登録者

Niu, W.,Chen, Z.,Bush-Pelc, L.A.,Bah, A.,Gandhi, P.S.,Di Cera, E. (登録日: 2009-09-22, 公開日: 2009-10-20, 最終更新日: 2023-09-06)

主引用文献

Niu, W.,Chen, Z.,Bush-Pelc, L.A.,Bah, A.,Gandhi, P.S.,Di Cera, E.
Mutant N143P reveals how Na+ activates thrombin
J.Biol.Chem., 284:36175-36185, 2009

PubMed Abstract: The molecular mechanism of thrombin activation by Na(+) remains elusive. Its kinetic formulation requires extension of the classical Botts-Morales theory for the action of a modifier on an enzyme to correctly account for the contribution of the E*, E, and E:Na(+) forms. The extended scheme establishes that analysis of k(cat) unequivocally identifies allosteric transduction of Na(+) binding into enhanced catalytic activity. The thrombin mutant N143P features no Na(+)-dependent enhancement of k(cat) yet binds Na(+) with an affinity comparable to that of wild type. Crystal structures of the mutant in the presence and absence of Na(+) confirm that Pro(143) abrogates the important H-bond between the backbone N atom of residue 143 and the carbonyl O atom of Glu(192), which in turn controls the orientation of the Glu(192)-Gly(193) peptide bond and the correct architecture of the oxyanion hole. We conclude that Na(+) activates thrombin by securing the correct orientation of the Glu(192)-Gly(193) peptide bond, which is likely flipped in the absence of cation. Absolute conservation of the 143-192 H-bond in trypsin-like proteases and the importance of the oxyanion hole in protease function suggest that this mechanism of Na(+) activation is present in all Na(+)-activated trypsin-like proteases.

PubMed: 19846563
DOI: 10.1074/jbc.M109.069500

実験手法

X-RAY DIFFRACTION (2.4 Å)