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

被引：22

作者：

Alligood, KJ ^{[1
]}

Charifson, PS ^{[1
]}

Crosby, R ^{[1
]}

Consler, TG ^{[1
]}

Feldman, PL ^{[1
]}

Gampe, RT ^{[1
]}

Gilmer, TM ^{[1
]}

Jordan, SR ^{[1
]}

Milstead, MW ^{[1
]}

Mohr, C ^{[1
]}

Peel, MR ^{[1
]}

Rocque, W ^{[1
]}

Rodriguez, M ^{[1
]}

Rusnak, DW ^{[1
]}

Shewchuk, LM ^{[1
]}

Sternbach, DD ^{[1
]}

机构：

[1] Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 10期

关键词：

D O I：

10.1016/S0960-894X(98)00195-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：1189 / 1194

页数：6

共 32 条

[1] CATALYTIC ACTIVITY OF THE SH2 DOMAIN OF HUMAN PP6O(C-SRC-CENTER-DOT), EVIDENCE FROM NMR, MASS-SPECTROMETRY, SITE-DIRECTED MUTAGENESIS AND KINETIC-STUDIES FOR AN INHERENT PHOSPHATASE-ACTIVITY [J].