1u59

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[[Image:1u59.jpg|left|200px]]
[[Image:1u59.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 1u59 |SIZE=350|CAPTION= <scene name='initialview01'>1u59</scene>, resolution 2.30&Aring;
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The line below this paragraph, containing "STRUCTURE_1u59", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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|GENE= ZAP70, SRK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=
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{{STRUCTURE_1u59| PDB=1u59 | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u59 OCA], [http://www.ebi.ac.uk/pdbsum/1u59 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1u59 RCSB]</span>
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'''Crystal Structure of the ZAP-70 Kinase Domain in Complex with Staurosporine'''
'''Crystal Structure of the ZAP-70 Kinase Domain in Complex with Staurosporine'''
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[[Category: Strickler, J E.]]
[[Category: Strickler, J E.]]
[[Category: Weaver, D T.]]
[[Category: Weaver, D T.]]
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[[Category: transferase]]
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[[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 Mon Mar 31 00:05:34 2008''
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Revision as of 07:46, 3 May 2008

Image:1u59.jpg

Template:STRUCTURE 1u59

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


Overview

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.

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 Page seeded by OCA on Sat May 3 10:46:15 2008

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