1XJD

Crystal Structure of PKC-theta complexed with Staurosporine at 2A resolution

1XJD の概要

• エントリーDOI: 10.2210/pdb1xjd/pdb
• 分子名称: Protein kinase C, theta type, STAUROSPORINE (3 entities in total)
• 機能のキーワード: kinase, pkc-theta, atp, amp, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41288.55

構造登録者

Xu, Z.B. (登録日: 2004-09-23, 公開日: 2004-10-19, 最終更新日: 2024-10-30)

主引用文献

Xu, Z.B.,Chaudhary, D.,Olland, S.,Wolfrom, S.,Czerwinski, R.,Malakian, K.,Lin, L.,Stahl, M.L.,Joseph-McCarthy, D.,Benander, C.,Fitz, L.,Greco, R.,Somers, W.S.,Mosyak, L.
Catalytic domain crystal structure of protein kinase C-theta (PKCtheta)
J.Biol.Chem., 279:50401-50409, 2004

PubMed Abstract: A member of the novel protein kinase C (PKC) subfamily, PKC, is an essential component of the T cell synapse and is required for optimal T cell activation and interleukin-2 production. Selective involvement of PKC in TCR signaling makes this enzyme an attractive therapeutic target in T cell-mediated disease processes. In this report we describe the crystal structure of the catalytic domain of PKC at 2.0-A resolution. Human recombinant PKC kinase domain was expressed in bacteria as catalytically active phosphorylated enzyme and co-crystallized with its subnanomolar, ATP site inhibitor staurosporine. The structure follows the classic bilobal kinase fold and shows the enzyme in its active conformation and phosphorylated state. Inhibitory interactions between conserved features of staurosporine and the ATP-binding cleft are accompanied by closing of the glycine-rich loop, which also maintains an inhibitory arrangement by blocking the phosphate recognition subsite. The two major phosphorylation sites, Thr-538 in the activation loop and Ser-695 in the hydrophobic motif, are both occupied in the structure, playing key roles in stabilizing active conformation of the enzyme and indicative of PKC autocatalytic phosphorylation and activation during bacterial expression. The PKC-staurosporine complex represents the first kinase domain crystal structure of any PKC isotypes to be determined and as such should provide valuable insight into PKC specificity and into rational drug design strategies for PKC selective leads.

PubMed: 15364937
DOI: 10.1074/jbc.M409216200

実験手法

X-RAY DIFFRACTION (2 Å)