二肽配体与src SH2结构域之间共价复合物的形成。

The formation of a covalent complex between a dipeptide ligand and the src SH2 domain.

作者信息

Alligood K J, Charifson P S, Crosby R, Consler T G, Feldman P L, Gampe R T, Gilmer T M, Jordan S R, Milstead M W, Mohr C, Peel M R, Rocque W, Rodriguez M, Rusnak D W, Shewchuk L M, Sternbach D D

机构信息

Glaxo Wellcome, Inc., Research Triangle Park, North Carolina 27709, USA.

出版信息

Bioorg Med Chem Lett. 1998 May 19;8(10):1189-94. doi: 10.1016/s0960-894x(98)00195-4.

DOI:10.1016/s0960-894x(98)00195-4

PMID:9871733

Abstract

The X-ray crystal structure of the src SH2 domain revealed the presence of a thiol residue (Cys 188) located proximal to the phosphotyrosine portion of a dipeptide ligand. An aldehyde bearing ligand (1) was designed to position an electrophilic carbonyl group in the vicinity of the thiol. X-ray crystallographic and NMR examination of the complex formed between (1) and the src SH2 domain revealed a hemithioacetal formed by addition of the thiol to the aldehyde group with an additional stabilizing hydrogen bond between the acetal hydroxyl and a backbone carbonyl.

摘要

src SH2结构域的X射线晶体结构显示，在二肽配体的磷酸酪氨酸部分附近存在一个硫醇残基（半胱氨酸188）。设计了一种带有醛基的配体（1），使亲电羰基位于硫醇附近。对（1）与src SH2结构域形成的复合物进行X射线晶体学和核磁共振检查发现，硫醇与醛基加成形成了半硫代缩醛，缩醛羟基与主链羰基之间还存在一个额外的稳定氢键。