1qad
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /><applet load="1qad" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qad, resolution 1.80Å" /> '''Crystal Structure of...)
Next diff →
Revision as of 22:24, 20 November 2007
|
Crystal Structure of the C-Terminal SH2 Domain of the P85 alpha Regulatory Subunit of Phosphoinositide 3-Kinase: An SH2 domain mimicking its own substrate
Overview
The binding properties of Src homology-2 (SH2) domains to phosphotyrosine, (pY)-containing peptides have been studied in recent years with the, elucidation of a large number of crystal and solution structures. Taken, together, these structures suggest a general mode of binding of, pY-containing peptides, explain the specificities of different SH2, domains, and may be used to design inhibitors of pY binding by SH2, domain-containing proteins. We now report the crystal structure to 1.8 A, resolution of the C-terminal SH2 domain (C-SH2) of the P85alpha regulatory, subunit of phosphoinositide 3-kinase (PI3 K). Surprisingly, the, carboxylate group of Asp2 from a neighbouring molecule occupies the, phosphotyrosine binding site and interacts with Arg18 (alphaA2) and Arg36, (betaB5), in a similar manner to the phosphotyrosine-protein interactions, seen in structures of other SH2 domains complexed with pY peptides. It is, the first example of a non-phosphate-containing, non-aromatic mimetic of, phosphotyrosine binding to SH2 domains, and this could have implications, for the design of substrate analogues and inhibitors. Overall, the crystal, structure closely resembles the solution structure, but a number of loops, which demonstrate mobility in solution are well defined by the crystal, packing. C-SH2 has adopted a binding conformation reminiscent of the, ligand bound N-terminal SH2 domain of PI3K, apparently induced by the, substrate mimicking of a neighbouring molecule in the crystal.
About this Structure
1QAD is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
Reference
Crystal structure of the C-terminal SH2 domain of the p85alpha regulatory subunit of phosphoinositide 3-kinase: an SH2 domain mimicking its own substrate., Hoedemaeker FJ, Siegal G, Roe SM, Driscoll PC, Abrahams JP, J Mol Biol. 1999 Oct 1;292(4):763-70. PMID:10525402
Page seeded by OCA on Wed Nov 21 00:31:31 2007
