1opl
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(New page: 200px<br /> <applet load="1opl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1opl, resolution 3.42Å" /> '''Structural basis fo...)
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Revision as of 16:28, 12 November 2007
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Structural basis for the auto-inhibition of c-Abl tyrosine kinase
Contents |
Overview
c-Abl is normally regulated by an autoinhibitory mechanism, the disruption, of which leads to chronic myelogenous leukemia. The details of this, mechanism have been elusive because c-Abl lacks a phosphotyrosine residue, that triggers the assembly of the autoinhibited form of the closely, related Src kinases by internally engaging the SH2 domain. Crystal, structures of c-Abl show that the N-terminal myristoyl modification of, c-Abl 1b binds to the kinase domain and induces conformational changes, that allow the SH2 and SH3 domains to dock onto it. Autoinhibited c-Abl, forms an assembly that is strikingly similar to that of inactive Src, kinases but with specific differences that explain the differential, ability of the drug STI-571/Gleevec/imatinib (STI-571) to inhibit the, catalytic activity of Abl, but not that of c-Src.
Disease
Known diseases associated with this structure: Leukemia, Philadelphia chromosome-positive, resistant to imatinib OMIM:[189980]
About this Structure
1OPL is a Single protein structure of sequence from Homo sapiens with MYR and P16 as ligands. The following page contains interesting information on the relation of 1OPL with [Src Tyrosine Kinase]. 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 basis for the autoinhibition of c-Abl tyrosine kinase., Nagar B, Hantschel O, Young MA, Scheffzek K, Veach D, Bornmann W, Clarkson B, Superti-Furga G, Kuriyan J, Cell. 2003 Mar 21;112(6):859-71. PMID:12654251
Page seeded by OCA on Mon Nov 12 18:35:13 2007
