1y57

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{{STRUCTURE_1y57| PDB=1y57 | SCENE= }}
{{STRUCTURE_1y57| PDB=1y57 | SCENE= }}
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'''Structure of unphosphorylated c-Src in complex with an inhibitor'''
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===Structure of unphosphorylated c-Src in complex with an inhibitor===
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==Overview==
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The regulation of the activity of Abl and Src family tyrosine kinases is mediated by intramolecular interactions between the SH3, SH2, and kinase (SH1) domains. We have determined the crystal structure of an unphosphorylated form of c-Src in which the SH2 domain is not bound to the C-terminal tail. This results in an open structure where the kinase domain adopts an active conformation and the C terminus binds within a hydrophobic pocket in the C-terminal lobe. NMR binding studies support the hypothesis that an N-terminal myristate could bind in this pocket, as observed for Abl, suggesting that c-Src may also be regulated by myristate binding. In addition, the structure contains a des-methyl analog of the antileukemia drug imatinib (STI571; Gleevec). This structure reveals why the drug shows a low affinity for active kinase conformations, contributing to its excellent kinase selectivity profile.
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(as it appears on PubMed at http://www.pubmed.gov), where 15939018 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15939018}}
==Disease==
==Disease==
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[[Category: Sh2]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:16:54 2008''

Revision as of 01:16, 28 July 2008

Image:1y57.png

Template:STRUCTURE 1y57

Contents

Structure of unphosphorylated c-Src in complex with an inhibitor

Template:ABSTRACT PUBMED 15939018

Disease

Known disease associated with this structure: Colon cancer, advanced OMIM:[190090]

About this Structure

1Y57 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The crystal structure of a c-Src complex in an active conformation suggests possible steps in c-Src activation., Cowan-Jacob SW, Fendrich G, Manley PW, Jahnke W, Fabbro D, Liebetanz J, Meyer T, Structure. 2005 Jun;13(6):861-71. PMID:15939018

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