1u59

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{{STRUCTURE_1u59| PDB=1u59 | SCENE= }}
{{STRUCTURE_1u59| PDB=1u59 | SCENE= }}
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'''Crystal Structure of the ZAP-70 Kinase Domain in Complex with Staurosporine'''
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===Crystal Structure of the ZAP-70 Kinase Domain in Complex with Staurosporine===
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==Overview==
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The ZAP-70 tyrosine kinase plays a critical role in T cell activation and the immune response and therefore is a logical target for immunomodulatory therapies. Although the crystal structure of the tandem Src homology-2 domains of human ZAP-70 in complex with a peptide derived from the zeta subunit of the T cell receptor has been reported (Hatada, M. H., Lu, X., Laird, E. R., Green, J., Morgenstern, J. P., Lou, M., Marr, C. S., Phillips, T. B., Ram, M. K., Theriault, K., Zoller, M. J., and Karas, J. L. (1995) Nature 377, 32-38), the structure of the kinase domain has been elusive to date. We crystallized and determined the three-dimensional structure of the catalytic subunit of ZAP-70 as a complex with staurosporine to 2.3 A resolution, utilizing an active kinase domain containing residues 327-606 identified by systematic N- and C-terminal truncations. The crystal structure shows that this ZAP-70 kinase domain is in an active-like conformation despite the lack of tyrosine phosphorylation in the activation loop. The unique features of the ATP-binding site, identified by structural and sequence comparison with other kinases, will be useful in the design of ZAP-70-selective inhibitors.
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(as it appears on PubMed at http://www.pubmed.gov), where 15292186 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15292186}}
==About this Structure==
==About this Structure==
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[[Category: Weaver, D T.]]
[[Category: Weaver, D T.]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:46:15 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:48:18 2008''

Revision as of 10:48, 27 July 2008

Image:1u59.png

Template:STRUCTURE 1u59

Crystal Structure of the ZAP-70 Kinase Domain in Complex with Staurosporine

Template:ABSTRACT PUBMED 15292186

About this Structure

1U59 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The three-dimensional structure of the ZAP-70 kinase domain in complex with staurosporine: implications for the design of selective inhibitors., Jin L, Pluskey S, Petrella EC, Cantin SM, Gorga JC, Rynkiewicz MJ, Pandey P, Strickler JE, Babine RE, Weaver DT, Seidl KJ, J Biol Chem. 2004 Oct 8;279(41):42818-25. Epub 2004 Jul 29. PMID:15292186

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