Protein Science Laboratory, UCLA/Orthopaedic Hospital, Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095-1795, USA.
Front Biosci (Landmark Ed). 2012 Jun 1;17(7):2476-94. doi: 10.2741/4066.
Factor VII (FVII) consists of an N-terminal gamma-carboxyglutamic acid domain followed by two epidermal growth factor-like (EGF1 and EGF2) domains and the C-terminal protease domain. Activation of FVII results in a two-chain FVIIa molecule consisting of a light chain (Gla-EGF1-EGF2 domains) and a heavy chain (protease domain) held together by a single disulfide bond. During coagulation, the complex of tissue factor (TF, a transmembrane glycoprotein) and FVIIa activates factor IX (FIX) and factor X (FX). FVIIa is structurally "zymogen-like" and when bound to TF, it is more "active enzyme-like." FIX and FX share structural homology with FVII. Three structural biology aspects of FVIIa/TF are presented in this review. One, regions in soluble TF (sTF) that interact with FVIIa as well as mapping of Ca2+, Mg2+, Na+ and Zn2+ sites in FVIIa and their functions; two, modeled interactive regions of Gla and EGF1 domains of FXa and FIXa with FVIIa/sTF; and three, incompletely formed oxyanion hole in FVIIa/sTF and its induction by substrate/inhibitor. Finally, an overview of the recognition elements in TF pathway inhibitor is provided.
因子 VII（FVII）由一个 N 端γ-羧基谷氨酸结构域组成，后面跟着两个表皮生长因子样（EGF1 和 EGF2）结构域和 C 端蛋白酶结构域。FVII 的激活导致由轻链（Gla-EGF1-EGF2 结构域）和重链（蛋白酶结构域）组成的双链 FVIIa 分子，它们通过一个二硫键连接在一起。在凝血过程中，组织因子（TF，一种跨膜糖蛋白）和 FVIIa 的复合物激活因子 IX（FIX）和因子 X（FX）。FVIIa 在结构上类似于“酶原”，当与 TF 结合时，它更像“活性酶”。FIX 和 FX 与 FVII 具有结构同源性。本文综述了 FVIIa/TF 的三个结构生物学方面。一是可溶性 TF（sTF）中与 FVIIa 相互作用的区域，以及 FVIIa 中 Ca2+、Mg2+、Na+和 Zn2+位点的作图及其功能；二是 FXa 和 FIXa 的 Gla 和 EGF1 结构域与 FVIIa/sTF 的模拟相互作用区域；三是 FVIIa/sTF 中不完全形成的氧阴离子空洞及其被底物/抑制剂诱导。最后，提供了 TF 途径抑制剂的识别元件概述。
