2oiq: Difference between revisions
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[[Image:2oiq.gif|left|200px]] | [[Image:2oiq.gif|left|200px]] | ||
'''Crystal Structure of chicken c-Src kinase domain in complex with the cancer drug imatinib.''' | {{Structure | ||
|PDB= 2oiq |SIZE=350|CAPTION= <scene name='initialview01'>2oiq</scene>, resolution 2.07Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=STI:4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE'>STI</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] | |||
|GENE= SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus]) | |||
}} | |||
'''Crystal Structure of chicken c-Src kinase domain in complex with the cancer drug imatinib.''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2OIQ is a [ | 2OIQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OIQ OCA]. | ||
==Reference== | ==Reference== | ||
c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty., Seeliger MA, Nagar B, Frank F, Cao X, Henderson MN, Kuriyan J, Structure. 2007 Mar;15(3):299-311. PMID:[http:// | c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty., Seeliger MA, Nagar B, Frank F, Cao X, Henderson MN, Kuriyan J, Structure. 2007 Mar;15(3):299-311. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17355866 17355866] | ||
[[Category: Gallus gallus]] | [[Category: Gallus gallus]] | ||
[[Category: Non-specific protein-tyrosine kinase]] | [[Category: Non-specific protein-tyrosine kinase]] | ||
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[[Category: src]] | [[Category: src]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:00:14 2008'' | ||
Revision as of 16:00, 20 March 2008
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| 2oiq, resolution 2.07Å | |||||||||||||
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| Ligands: | STI and GOL | ||||||||||||
| Gene: | SRC (Gallus gallus) | ||||||||||||
| Activity: | Non-specific protein-tyrosine kinase, with EC number 2.7.10.2 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Crystal Structure of chicken c-Src kinase domain in complex with the cancer drug imatinib.
Overview
The cancer drug imatinib inhibits the tyrosine kinases c-Abl, c-Kit, and the PDGF receptor. Imatinib is less effective against c-Src, which is difficult to understand because residues interacting with imatinib in crystal structures of Abl and c-Kit are conserved in c-Src. The crystal structure of the c-Src kinase domain in complex with imatinib closely resembles that of Abl*imatinib and c-Kit*imatinib, and differs significantly from the inactive "Src/CDK" conformation of the Src family kinases. Attempts to increase the affinity of c-Src for imatinib by swapping residues with the corresponding residues in Abl have not been successful, suggesting that the thermodynamic penalty for adoption of the imatinib-binding conformation by c-Src is distributed over a broad region of the structure. Two mutations that are expected to destabilize the inactive Src/CDK conformation increase drug sensitivity 15-fold, suggesting that the free-energy balance between different inactive states is a key to imatinib binding.
About this Structure
2OIQ is a Single protein structure of sequence from Gallus gallus. Full crystallographic information is available from OCA.
Reference
c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty., Seeliger MA, Nagar B, Frank F, Cao X, Henderson MN, Kuriyan J, Structure. 2007 Mar;15(3):299-311. PMID:17355866
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