2SEM

SEM5 SH3 DOMAIN COMPLEXED WITH PEPTOID INHIBITOR

Summary for 2SEM

• Entry DOI: 10.2210/pdb2sem/pdb
• Related PRD ID: PRD_000245
• Descriptor: PROTEIN (SEX MUSCLE ABNORMAL PROTEIN 5), PROTEIN (SH3 PEPTOID INHIBITOR) (3 entities in total)
• Functional Keywords: sh3 domain, inhibitors, peptoids, protein-protein recognition, proline-rich motifs, signal transduction, signaling protein, signaling protein-inhibitor complex, signaling protein/inhibitor
• Biological source: Caenorhabditis elegans; More
• Total number of polymer chains: 4
• Total formula weight: 15891.70

Authors

Nguyen, J.T.,Turck, C.W.,Cohen, F.E.,Zuckermann, R.N.,Lim, W.A. (deposition date: 1998-11-02, release date: 1999-01-06, Last modification date: 2023-11-15)

Primary citation

Nguyen, J.T.,Turck, C.W.,Cohen, F.E.,Zuckermann, R.N.,Lim, W.A.
Exploiting the basis of proline recognition by SH3 and WW domains: design of N-substituted inhibitors.
Science, 282:2088-2092, 1998

PubMed Abstract: Src homology 3 (SH3) and WW protein interaction domains bind specific proline-rich sequences. However, instead of recognizing critical prolines on the basis of side chain shape or rigidity, these domains broadly accepted amide N-substituted residues. Proline is apparently specifically selected in vivo, despite low complementarity, because it is the only endogenous N-substituted amino acid. This discriminatory mechanism explains how these domains achieve specific but low-affinity recognition, a property that is necessary for transient signaling interactions. The mechanism can be exploited: screening a series of ligands in which key prolines were replaced by nonnatural N-substituted residues yielded a ligand that selectively bound the Grb2 SH3 domain with 100 times greater affinity.

PubMed: 9851931
DOI: 10.1126/science.282.5396.2088

Experimental method

X-RAY DIFFRACTION (2.2 Å)