1yoj
From Proteopedia
(New page: 200px<br /> <applet load="1yoj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yoj, resolution 1.95Å" /> '''Crystal structure o...) |
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| - | [[Image:1yoj.gif|left|200px]]<br /> | + | [[Image:1yoj.gif|left|200px]]<br /><applet load="1yoj" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1yoj, resolution 1.95Å" /> | caption="1yoj, resolution 1.95Å" /> | ||
'''Crystal structure of Src kinase domain'''<br /> | '''Crystal structure of Src kinase domain'''<br /> | ||
==Overview== | ==Overview== | ||
| - | c-Src was the first proto-oncoprotein to be identified, and has become the | + | c-Src was the first proto-oncoprotein to be identified, and has become the focus of many drug discovery programs. Src structures of a major inactive form have shown how the protein kinase is rigidified by several interdomain interactions; active configurations of Src are generated by release from this "assembled" or "bundled" form. Despite the importance of Src as a drug target, there is relatively little structural information available regarding the presumably more flexible active forms. Here we report three crystal structures of a dimeric active c-Src kinase domain, in an apo and two ligand complexed forms, with resolutions ranging from 2.9A to 1.95A. The structures show how the kinase domain, in the absence of the rigidifying interdomain interactions of the inactivation state, adopts a more open and flexible conformation. The ATP site inhibitor CGP77675 binds to the protein kinase with canonical hinge hydrogen bonds and also to the c-Src specific threonine 340. In contrast to purvalanol B binding in CDK2, purvalanol A binds in c-Src with a conformational change in a more open ATP pocket. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1YOJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http:// | + | 1YOJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YOJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
| - | [[Category: Breitenlechner, C | + | [[Category: Breitenlechner, C B.]] |
| - | [[Category: Engh, R | + | [[Category: Engh, R A.]] |
[[Category: Greiter, E.]] | [[Category: Greiter, E.]] | ||
[[Category: Honold, K.]] | [[Category: Honold, K.]] | ||
[[Category: Huber, R.]] | [[Category: Huber, R.]] | ||
| - | [[Category: Kairies, N | + | [[Category: Kairies, N A.]] |
[[Category: Koch, S.]] | [[Category: Koch, S.]] | ||
[[Category: Koll, H.]] | [[Category: Koll, H.]] | ||
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[[Category: protein tyrosine kinase]] | [[Category: protein tyrosine kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:07:31 2008'' |
Revision as of 14:07, 21 February 2008
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Crystal structure of Src kinase domain
Contents |
Overview
c-Src was the first proto-oncoprotein to be identified, and has become the focus of many drug discovery programs. Src structures of a major inactive form have shown how the protein kinase is rigidified by several interdomain interactions; active configurations of Src are generated by release from this "assembled" or "bundled" form. Despite the importance of Src as a drug target, there is relatively little structural information available regarding the presumably more flexible active forms. Here we report three crystal structures of a dimeric active c-Src kinase domain, in an apo and two ligand complexed forms, with resolutions ranging from 2.9A to 1.95A. The structures show how the kinase domain, in the absence of the rigidifying interdomain interactions of the inactivation state, adopts a more open and flexible conformation. The ATP site inhibitor CGP77675 binds to the protein kinase with canonical hinge hydrogen bonds and also to the c-Src specific threonine 340. In contrast to purvalanol B binding in CDK2, purvalanol A binds in c-Src with a conformational change in a more open ATP pocket.
Disease
Known disease associated with this structure: Colon cancer, advanced OMIM:[190090]
About this Structure
1YOJ is a Single protein structure of sequence from Homo sapiens. 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
Crystal structures of active SRC kinase domain complexes., Breitenlechner CB, Kairies NA, Honold K, Scheiblich S, Koll H, Greiter E, Koch S, Schafer W, Huber R, Engh RA, J Mol Biol. 2005 Oct 21;353(2):222-31. PMID:16168436
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