1opl
From Proteopedia
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==Overview== | ==Overview== | ||
| - | c-Abl is normally regulated by an autoinhibitory mechanism, the disruption | + | 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== | ==Disease== | ||
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[[Category: Superti-Furga, G.]] | [[Category: Superti-Furga, G.]] | ||
[[Category: Veach, D.]] | [[Category: Veach, D.]] | ||
| - | [[Category: Young, M | + | [[Category: Young, M A.]] |
[[Category: MYR]] | [[Category: MYR]] | ||
[[Category: P16]] | [[Category: P16]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:20:13 2008'' |
Revision as of 12:20, 21 February 2008
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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 and 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
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