1u59

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spinqualitylabelsall models 1u59, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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.

Disease

Known diseases associated with this structure: Selective T-cell defect OMIM:[176947]

About this Structure

1U59 is a Single protein structure of sequence from Homo sapiens with STU 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.

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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