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1oo4

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Revision as of 11:13, 20 March 2008 by OCA (Talk | contribs)
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PDB ID 1oo4

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P395S mutant of the p85 regulatory subunit of the N-terminal src homology 2 domain of PI3-Kinase complexed to a peptide derived from PDGFr


Overview

Understanding the specificity of Src homology 2 (SH2) domains is important because of their critical role in cell signaling. Previous genetic analysis has characterized mutants of the N-terminal src homology 2 (SH2) domain of the p85 subunit of phosphoinositide 3-kinase (PI3K). The P395S mutant exhibits a specificity for phosphopeptide binding different from that of the wild-type SH2. The P395S mutant has an increased affinity for the platelet-derived growth factor receptor (PDGFr) compared to polyomavirus middle T antigen (MT). Solution structures of the P395S mutant of the p85 N-SH2 alone and complexed to a PDGFr phosphopeptide were determined to explain the change in specificity. Chemical shift perturbations caused by different peptides were compared for mutant and wild-type structures. The results show that the single P395S mutation has broad effects on the structure. Furthermore, they provide a rationale for the observed changes in binding preference.

About this Structure

1OO4 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

Reference

Nuclear magnetic resonance structure of the P395S mutant of the N-SH2 domain of the p85 subunit of PI3 kinase: an SH2 domain with altered specificity., Gunther UL, Weyrauch B, Zhang X, Schaffhausen B, Biochemistry. 2003 Sep 30;42(38):11120-7. PMID:14503862

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