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
BOERNER, RJ
CONSLER, TG
GAMPE, RT
WEIGL, D
WILLARD, DH
DAVIS, DG
EDISON, AM
LOGANZO, F
KASSEL, DB
XU, RX
PATEL, IR
ROBBINS, JS
LANSING, T
GILMER, TM
LUTHER, MA
KNIGHT, WB
[J]. BIOCHEMISTRY, 1995, 34 (46) : 15351 - 15358
[2] EXTENSION OF MOLECULAR REPLACEMENT - A NEW SEARCH STRATEGY BASED ON PATTERSON CORRELATION REFINEMENT
BRUNGER, AT
[J]. ACTA CRYSTALLOGRAPHICA SECTION A, 1990, 46 : 46 - 57
[3] NONHYDROLYZABLE PHOSPHOTYROSYL MIMETICS FOR THE PREPARATION OF PHOSPHATASE-RESISTANT SH2 DOMAIN INHIBITORS
BURKE, TR
SMYTH, MS
OTAKA, A
NOMIZU, M
ROLLER, PP
WOLF, G
CASE, R
SHOELSON, SE
[J]. BIOCHEMISTRY, 1994, 33 (21) : 6490 - 6494
[4] Peptide ligands of pp60(c-src) SH2 domains: A thermodynamic and structural study
Charifson, PS
Shewchuk, LM
Rocque, W
Hummel, CW
Jordan, SR
Mohr, C
Pacofsky, GJ
Peel, MR
Rodriguez, M
Sternbach, DD
Consler, TG
[J]. BIOCHEMISTRY, 1997, 36 (21) : 6283 - 6293
[5] STABLE ASSOCIATION OF PP60(SRC) AND PP59(FYN) WITH THE FOCAL ADHESION-ASSOCIATED PROTEIN-TYROSINE KINASE, PP125(FAK)
COBB, BS
SCHALLER, MD
LEU, TH
PARSONS, JT
[J]. MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (01) : 147 - 155
[6] A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation
Dikic, I
Tokiwa, G
Lev, S
Courtneidge, SA
Schlessinger, J
[J]. NATURE, 1996, 383 (6600) : 547 - 550
[7] A TARGET FOR SRC IN MITOSIS
FUMAGALLI, S
TOTTY, NF
HSUAN, JJ
COURTNEIDGE, SA
[J]. NATURE, 1994, 368 (6474) : 871 - 874
[8] GILMER T, 1994, J BIOL CHEM, V269, P31711
[9] Covalent binding of catechols to Src family SH2 domains
Jagoe, CT
Kreifels, SE
Li, JM
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (02) : 113 - 116
[10] KRANTZ A, 1992, ADV MED CHEM, V1, P235

← 1 2 3 4 →