锯鳞蝰蛇毒液中胶原蛋白受体（GPIa/IIa）拮抗剂EMS16的表征及初步晶体学研究

Characterization and preliminary crystallographic studies of EMS16, an antagonist of collagen receptor (GPIa/IIa) from the venom of Echis multisquamatus.

作者信息

Okuda Daiju, Horii Katsunori, Mizuno Hiroshi, Morita Takashi

机构信息

Department of Biochemistry, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose, Tokyo, 204-8588.

出版信息

J Biochem. 2003 Jul;134(1):19-23. doi: 10.1093/jb/mvg108.

DOI:10.1093/jb/mvg108

PMID:12944366

Abstract

EMS16 is a member of the snake venom-derived C-type lectin family of proteins (CLPs) found in the venom of Echis multisquamatus. It binds to glycoprotein Ia/IIa (integrin alpha2beta1), a major collagen receptor of platelets, acting as a potent antagonist of platelet aggregation and cell migration. Amino acid sequencing and cDNA cloning of EMS16 have revealed that it is composed of an A chain of 134 amino acid residues and a B chain of 128 residues. Crystals of EMS16 belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 46.57, b = 59.93, and c = 115.74 A, and diffract to a resolution of 1.9 A. Phase determination is underway by means of molecular replacement with the structure of blood coagulation factor IX-binding protein (IX-bp) from habu snake venom (PDB code 1bj3) as the search model.

摘要

EMS16是在多鳞蝰蛇毒液中发现的蛇毒衍生C型凝集素蛋白家族（CLPs）的成员。它与糖蛋白Ia/IIa（整合素α2β1）结合，糖蛋白Ia/IIa是血小板的主要胶原受体，它作为血小板聚集和细胞迁移的有效拮抗剂。EMS16的氨基酸测序和cDNA克隆表明，它由一条含134个氨基酸残基的A链和一条含128个残基的B链组成。EMS16的晶体属于空间群P2(1)2(1)2(1)，晶胞参数a = 46.57，b = 59.93，c = 115.74 Å，衍射分辨率为1.9 Å。目前正在通过分子置换法进行相位测定，以来自竹叶青蛇毒液的凝血因子IX结合蛋白（IX-bp）的结构（PDB代码1bj3）作为搜索模型。