1ir3
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /> <applet load="1ir3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ir3, resolution 1.9Å" /> '''PHOSPHORYLATED INSUL...)
Next diff →
Revision as of 15:27, 12 November 2007
|
PHOSPHORYLATED INSULIN RECEPTOR TYROSINE KINASE IN COMPLEX WITH PEPTIDE SUBSTRATE AND ATP ANALOG
Contents |
Overview
The crystal structure of the phosphorylated, activated form of the insulin, receptor tyrosine kinase in complex with a peptide substrate and an ATP, analog has been determined at 1.9 A resolution. The activation loop, (A-loop) of the kinase undergoes a major conformational change upon, autophosphorylation of Tyr1158, Tyr1162 and Tyr1163 within the loop, resulting in unrestricted access of ATP and protein substrates to the, kinase active site. Phosphorylated Tyr1163 (pTyr1163) is the key, phosphotyrosine in stabilizing the conformation of the tris-phosphorylated, A-loop, whereas pTyr1158 is completely solvent-exposed, suggesting an, availability for interaction with downstream signaling proteins. The, YMXM-containing peptide substrate binds as a short anti-parallel, beta-strand to the C-terminal end of the A-loop, with the methionine side, chains occupying two hydrophobic pockets on the C-terminal lobe of the, kinase. The structure thus reveals the molecular basis for insulin, receptor activation via autophosphorylation, and provides insights into, tyrosine kinase substrate specificity and the mechanism of, phosphotransfer.
Disease
Known diseases associated with this structure: Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[147670], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[147670], Leprechaunism OMIM:[147670], Rabson-Mendenhall syndrome OMIM:[147670]
About this Structure
1IR3 is a Single protein structure of sequence from Homo sapiens with MG and ANP as ligands. 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
Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog., Hubbard SR, EMBO J. 1997 Sep 15;16(18):5572-81. PMID:9312016
Page seeded by OCA on Mon Nov 12 17:33:40 2007
