1opk
Structural basis for the auto-inhibition of c-Abl tyrosine kinase
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| , resolution 1.80Å | |||||||
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| Ligands: | , and | ||||||
| Gene: | ABL1 (Mus musculus) | ||||||
| Activity: | Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
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.
About this StructureAbout this Structure
1OPK is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
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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