2BVA

Crystal structure of the human P21-activated kinase 4

2BVA の概要

• エントリーDOI: 10.2210/pdb2bva/pdb
• 分子名称: P21-ACTIVATED KINASE 4 (2 entities in total)
• 機能のキーワード: protein kinase, ste20, pak4, atp-binding, transferase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66022.74

構造登録者

Debreczeni, J.E.,Bunkoczi, G.,Eswaran, J.,Filippakopoulos, P.,Das, S.,Fedorov, O.,Sundstrom, M.,Arrowsmith, C.,Edwards, A.,von Delft, F.,Knapp, S. (登録日: 2005-06-23, 公開日: 2005-07-14, 最終更新日: 2024-11-13)

主引用文献

Eswaran, J.,Lee, W.H.,Debreczeni, J.E.,Filippakopoulos, P.,Turnbull, A.,Fedorov, O.,Deacon, S.W.,Peterson, J.R.,Knapp, S.
Crystal Structures of the P21-Activated Kinases Pak4, Pak5, and Pak6 Reveal Catalytic Domain Plasticity of Active Group II Paks.
Structure, 15:201-, 2007

PubMed Abstract: p21-activated kinases have been classified into two groups based on their domain architecture. Group II PAKs (PAK4-6) regulate a wide variety of cellular functions, and PAK deregulation has been linked to tumor development. Structural comparison of five high-resolution structures comprising all active, monophosphorylated group II catalytic domains revealed a surprising degree of domain plasticity, including a number of catalytically productive and nonproductive conformers. Rearrangements of helix alphaC, a key regulatory element of kinase function, resulted in an additional helical turn at the alphaC N terminus and a distortion of its C terminus, a movement hitherto unseen in protein kinases. The observed structural changes led to the formation of interactions between conserved residues that structurally link the glycine-rich loop, alphaC, and the activation segment and firmly anchor alphaC in an active conformation. Inhibitor screening identified six potent PAK inhibitors from which a tri-substituted purine inhibitor was cocrystallized with PAK4 and PAK5.

PubMed: 17292838
DOI: 10.1016/J.STR.2007.01.001

実験手法

X-RAY DIFFRACTION (2.3 Å)