1ksw: Difference between revisions
New page: left|200px<br /> <applet load="1ksw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ksw, resolution 2.8Å" /> '''Structure of Human c... |
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[[Image:1ksw.gif|left|200px]]<br /> | [[Image:1ksw.gif|left|200px]]<br /><applet load="1ksw" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1ksw" size=" | |||
caption="1ksw, resolution 2.8Å" /> | caption="1ksw, resolution 2.8Å" /> | ||
'''Structure of Human c-Src Tyrosine Kinase (Thr338Gly Mutant) in Complex with N6-benzyl ADP'''<br /> | '''Structure of Human c-Src Tyrosine Kinase (Thr338Gly Mutant) in Complex with N6-benzyl ADP'''<br /> | ||
==Overview== | ==Overview== | ||
The direct substrates of one protein kinase in a cell can be identified by | The direct substrates of one protein kinase in a cell can be identified by mutation of the ATP binding pocket to allow an unnatural ATP analog to be accepted exclusively by the engineered kinase. Here, we present structural and functional assessment of peptide specificity of mutant protein kinases with unnatural ATP analogs. The crystal structure (2.8 A resolution) of c-Src (T338G) with N(6)-(benzyl) ADP bound shows that the creation of a unique nucleotide binding pocket does not alter the phospho-acceptor binding site of the kinase. A panel of optimal peptide substrates of defined sequence, as well as a degenerate peptide library, was utilized to assess the phospho-acceptor specificity of the engineered "traceable" kinases. The specificity profiles for the mutant kinases were found to be identical to those of their wild-type counterparts. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1KSW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NBS as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | 1KSW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NBS:'>NBS</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1KSW OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
[[Category: Eck, M | [[Category: Eck, M J.]] | ||
[[Category: Huang, X.]] | [[Category: Huang, X.]] | ||
[[Category: Kyin, S.]] | [[Category: Kyin, S.]] | ||
[[Category: Liu, Y.]] | [[Category: Liu, Y.]] | ||
[[Category: Shah, K.]] | [[Category: Shah, K.]] | ||
[[Category: Shokat, K | [[Category: Shokat, K M.]] | ||
[[Category: Witucki, L | [[Category: Witucki, L A.]] | ||
[[Category: NBS]] | [[Category: NBS]] | ||
[[Category: atp]] | [[Category: atp]] | ||
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[[Category: sh3]] | [[Category: sh3]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:37:33 2008'' | ||
Revision as of 14:37, 21 February 2008
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Structure of Human c-Src Tyrosine Kinase (Thr338Gly Mutant) in Complex with N6-benzyl ADP
OverviewOverview
The direct substrates of one protein kinase in a cell can be identified by mutation of the ATP binding pocket to allow an unnatural ATP analog to be accepted exclusively by the engineered kinase. Here, we present structural and functional assessment of peptide specificity of mutant protein kinases with unnatural ATP analogs. The crystal structure (2.8 A resolution) of c-Src (T338G) with N(6)-(benzyl) ADP bound shows that the creation of a unique nucleotide binding pocket does not alter the phospho-acceptor binding site of the kinase. A panel of optimal peptide substrates of defined sequence, as well as a degenerate peptide library, was utilized to assess the phospho-acceptor specificity of the engineered "traceable" kinases. The specificity profiles for the mutant kinases were found to be identical to those of their wild-type counterparts.
DiseaseDisease
Known disease associated with this structure: Colon cancer, advanced OMIM:[190090]
About this StructureAbout this Structure
1KSW is a Single protein structure of sequence from Homo sapiens with as ligand. 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.
ReferenceReference
Mutant tyrosine kinases with unnatural nucleotide specificity retain the structure and phospho-acceptor specificity of the wild-type enzyme., Witucki LA, Huang X, Shah K, Liu Y, Kyin S, Eck MJ, Shokat KM, Chem Biol. 2002 Jan;9(1):25-33. PMID:11841936
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