2CLQ

Structure of mitogen-activated protein kinase kinase kinase 5

2CLQ の概要

• エントリーDOI: 10.2210/pdb2clq/pdb
• 分子名称: MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 5, STAUROSPORINE (3 entities in total)
• 機能のキーワード: transferase, metal-binding, apoptosis
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: Q99683
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67328.84

構造登録者

Bunkoczi, G.,Salah, E.,Fedorov, O.,Pike, A.,Gileadi, O.,von Delft, F.,Arrowsmith, C.,Edwards, A.,Sundstrom, M.,Weigelt, J.,Knapp, S. (登録日: 2006-04-28, 公開日: 2006-05-09, 最終更新日: 2024-05-01)

主引用文献

Bunkoczi, G.,Salah, E.,Filippakopoulos, P.,Fedorov, O.,Muller, S.,Sobott, F.,Parker, S.A.,Zhang, H.,Min, W.,Turk, B.E.,Knapp, S.
Structural and Functional Characterization of the Human Protein Kinase Ask1.
Structure, 15:1215-, 2007

PubMed Abstract: Apoptosis signal-regulating kinase 1 (ASK1) plays an essential role in stress and immune response and has been linked to the development of several diseases. Here, we present the structure of the human ASK1 catalytic domain in complex with staurosporine. Analytical ultracentrifugation (AUC) and crystallographic analysis showed that ASK1 forms a tight dimer (K(d) approximately 0.2 microM) interacting in a head-to-tail fashion. We found that the ASK1 phosphorylation motifs differ from known ASK1 phosphorylation sites but correspond well to autophosphorylation sites identified by mass spectrometry. Reporter gene assays showed that all three identified in vitro autophosphorylation sites (Thr813, Thr838, Thr842) regulate ASK1 signaling, but site-directed mutants showed catalytic activities similar to wild-type ASK1, suggesting a regulatory mechanism independent of ASK1 kinase activity. The determined high-resolution structure of ASK1 and identified ATP mimetic inhibitors will provide a first starting point for the further development of selective inhibitors.

PubMed: 17937911
DOI: 10.1016/J.STR.2007.08.011

実験手法

X-RAY DIFFRACTION (2.3 Å)