1U59

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

1U59 の概要

• エントリーDOI: 10.2210/pdb1u59/pdb
• 分子名称: Tyrosine-protein kinase ZAP-70, STAUROSPORINE (3 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P43403
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33714.13

構造登録者

Jin, L.,Pluskey, S.,Petrella, E.C.,Cantin, S.M.,Gorga, J.C.,Rynkiewicz, M.J.,Pandey, P.,Strickler, J.E.,Babine, R.E.,Weaver, D.T.,Seidl, K.J. (登録日: 2004-07-27, 公開日: 2004-08-17, 最終更新日: 2023-08-23)

主引用文献

Jin, L.,Pluskey, S.,Petrella, E.C.,Cantin, S.M.,Gorga, J.C.,Rynkiewicz, M.J.,Pandey, P.,Strickler, J.E.,Babine, R.E.,Weaver, D.T.,Seidl, K.J.
The Three-dimensional Structure of the ZAP-70 Kinase Domain in Complex with Staurosporine: IMPLICATIONS FOR THE DESIGN OF SELECTIVE INHIBITORS
J.Biol.Chem., 279:42818-42825, 2004

PubMed Abstract: 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.

PubMed: 15292186
DOI: 10.1074/jbc.M407096200

実験手法

X-RAY DIFFRACTION (2.3 Å)