1SKJ

COCRYSTAL STRUCTURE OF UREA-SUBSTITUTED PHOSPHOPEPTIDE COMPLEX

Summary for 1SKJ

• Entry DOI: 10.2210/pdb1skj/pdb
• Descriptor: PP60 V-SRC TYROSINE KINASE TRANSFORMING PROTEIN, 4-[3-CARBOXYMETHYL-3-(4-PHOSPHONOOXY-BENZYL)-UREIDO]-4-[(3-CYCLOHEXYL-PROPYL)-METHYL-CARBAMOYL]BUTYRIC ACID (3 entities in total)
• Functional Keywords: tyrosine-protein kinase, v-src sh2 domain, phosphotyrosine recognition domain, pp60 src sh2 domain, peptidomimetic, ureido
• Biological source: Rous sarcoma virus
• Total number of polymer chains: 1
• Total formula weight: 13479.07

Authors

Holland, D.R.,Rubin, J.R. (deposition date: 1997-09-18, release date: 1998-02-25, Last modification date: 2024-05-22)

Primary citation

Plummer, M.S.,Holland, D.R.,Shahripour, A.,Lunney, E.A.,Fergus, J.H.,Marks, J.S.,McConnell, P.,Mueller, W.T.,Sawyer, T.K.
Design, synthesis, and cocrystal structure of a nonpeptide Src SH2 domain ligand.
J.Med.Chem., 40:3719-3725, 1997

PubMed Abstract: The specific association of an SH2 domain with a phosphotyrosine (pTyr)-containing sequence of another protein precipitates a cascade of intracellular molecular interactions (signals) which effect a wide range of intracellular processes. The nonreceptor tyrosine kinase Src, which has been associated with breast cancer and osteoporosis, contains an SH2 domain. Inhibition of Src SH2-phosphoprotein interactions by small molecules will aid biological proof-of-concept studies which may lead to the development of novel therapeutic agents. Structure-based design efforts have focused on reducing the size and charge of Src SH2 ligands while increasing their ability to penetrate cells and reach the intracellular Src SH2 domain target. In this report we describe the synthesis, binding affinity, and Src SH2 cocrystal structure of a small, novel, nonpeptide, urea-containing SH2 domain ligand.

PubMed: 9371236
DOI: 10.1021/jm970402q

Experimental method

X-RAY DIFFRACTION (2 Å)