2sem | pdb_00002sem
SEM5 SH3 DOMAIN COMPLEXED WITH PEPTOID INHIBITOR
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Overview
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.
About this Structure
2SEM is a Single protein structure of sequence from Caenorhabditis elegans with ACE as ligand. Full crystallographic information is available from OCA.
Reference
Exploiting the basis of proline recognition by SH3 and WW domains: design of N-substituted inhibitors., Nguyen JT, Turck CW, Cohen FE, Zuckermann RN, Lim WA, Science. 1998 Dec 11;282(5396):2088-92. PMID:9851931
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