1a0n
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(New page: 200px<br /> <applet load="1a0n" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a0n" /> '''NMR STUDY OF THE SH3 DOMAIN FROM FYN PROTO-...)
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Revision as of 13:47, 12 November 2007
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NMR STUDY OF THE SH3 DOMAIN FROM FYN PROTO-ONCOGENE TYROSINE KINASE COMPLEXED WITH THE SYNTHETIC PEPTIDE P2L CORRESPONDING TO RESIDUES 91-104 OF THE P85 SUBUNIT OF PI3-KINASE, FAMILY OF 25 STRUCTURES
Overview
The interaction of the Fyn SH3 domain with the p85 subunit of PI3-kinase, is investigated using structural detail and thermodynamic data. The, solution structure complex of the SH3 domain with a proline-rich peptide, mimic of the binding site on the p85 subunit is described. This indicates, that the peptide binds as a poly(L-proline) type II helix. Circular, dichroism spectroscopic studies reveal that in the unbound state the, peptide exhibits no structure. Thermodynamic data for the binding of this, peptide to the SH3 domain suggest that the weak binding (approximately 31, microM) of this interaction is, in part, due to the entropically, unfavorable effect of helix formation (delta S0 = -78 J.mol-1.K-1)., Binding of the SH3 domain to the intact p85 subunit (minus its own SH3, domain) is tighter, and the entropic and enthalpic contributions are very, different from those given by the peptide interaction (delta S0 = +252, J.mol-1.K-1; delta H0 = +44 kJ.mol-1). From these dramatically different, thermodynamic measurements we are able to conclude that the interaction of, the proline-rich peptide does not effectively mimic the interaction of the, intact p85 subunit with the SH3 domain and suggest that other interactions, could be important.
About this Structure
1A0N is a Protein complex structure of sequences from Homo sapiens. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.
Reference
Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase., Renzoni DA, Pugh DJ, Siligardi G, Das P, Morton CJ, Rossi C, Waterfield MD, Campbell ID, Ladbury JE, Biochemistry. 1996 Dec 10;35(49):15646-53. PMID:8961927
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