2oiq
From Proteopedia
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|PDB= 2oiq |SIZE=350|CAPTION= <scene name='initialview01'>2oiq</scene>, resolution 2.07Å | |PDB= 2oiq |SIZE=350|CAPTION= <scene name='initialview01'>2oiq</scene>, resolution 2.07Å | ||
|SITE= | |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> | + | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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> |
| - | + | |ACTIVITY= <span class='plainlinks'>[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] </span> | |
|GENE= SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus]) | |GENE= SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oiq OCA], [http://www.ebi.ac.uk/pdbsum/2oiq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2oiq RCSB]</span> | ||
}} | }} | ||
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[[Category: Nagar, B.]] | [[Category: Nagar, B.]] | ||
[[Category: Seeliger, M A.]] | [[Category: Seeliger, M A.]] | ||
| - | [[Category: | + | [[Category: src,kinase,imatinib,inactive]] |
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:18:27 2008'' |
Revision as of 01:18, 31 March 2008
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| , resolution 2.07Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | SRC (Gallus gallus) | ||||||
| Activity: | Non-specific protein-tyrosine kinase, with EC number 2.7.10.2 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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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