THE FORMATION OF A COVALENT COMPLEX BETWEEN A DIPEPTIDE LIGAND AND THE SRC SH2 DOMAIN

Authors
ALLIGOOD KJ CHARIFSON PS CROSBY R CONSLER TG FELDMAN PL GAMPE RT GILMER TM JORDAN SR MILSTEAD MW MOHR C PEEL MR ROCQUE W RODRIGUEZ M RUSNAK DW SHEWCHUK LM STERNBACH DD
Citation
Kj. Alligood et al., THE FORMATION OF A COVALENT COMPLEX BETWEEN A DIPEPTIDE LIGAND AND THE SRC SH2 DOMAIN, Bioorganic & medicinal chemistry letters, 8(10), 1998, pp. 1189-1194
Citations number
32
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
8
Issue
10
Year of publication
1998
Pages
1189 - 1194
Database
ISI
SICI code
0960-894X(1998)8:10<1189:TFOACC>2.0.ZU;2-1
Abstract
The X-ray crystal structure of the src SH2 domain revealed the presenc e of a thiol residue (Cys 188) located proximal to the phosphotyrosine portion of a dipeptide ligand. An aldehyde bearing ligand (1) was des igned to position an electrophilic carbonyl group in the vicinity of t he thiol. X-ray crystallographic and NMR examination of the complex fo rmed between (1) and the src SH2 domain revealed a hemithioacetal form ed by addition of the thiol to the aldehyde group with an additional s tabilizing hydrogen bond between the acetal hydroxyl and a backbone ca rbonyl. (C) 1998 Elsevier Science Ltd. All rights reserved.