5VEE

PAK4 kinase domain in complex with FRAX486

5VEE の概要

• エントリーDOI: 10.2210/pdb5vee/pdb
• 関連するPDBエントリー: 5VED 5VEE
• 分子名称: Serine/threonine-protein kinase PAK 4, 6-(2,4-dichlorophenyl)-8-ethyl-2-{[3-fluoro-4-(piperazin-1-yl)phenyl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one (2 entities in total)
• 機能のキーワード: kinase, 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: 36539.14

構造登録者

Zhang, E.Y.,Ha, B.H.,Boggon, T.J. (登録日: 2017-04-04, 公開日: 2017-10-18, 最終更新日: 2024-10-09)

主引用文献

Zhang, E.Y.,Ha, B.H.,Boggon, T.J.
PAK4 crystal structures suggest unusual kinase conformational movements.
Biochim. Biophys. Acta, 1866:356-365, 2018

PubMed Abstract: In order for protein kinases to exchange nucleotide they must open and close their catalytic cleft. These motions are associated with rotations of the N-lobe, predominantly around the 'hinge region'. We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077). We find an unusual motion between the N-lobe and C-lobe of PAK4 that manifests as a partial unwinding of helix αC. Principal component analysis of the crystal structures rationalizes these movements into three major states, and analysis of the kinase hydrophobic spines indicates concerted movements that create an accessible back pocket cavity. The conformational changes that we observe for PAK4 differ from previous descriptions of kinase motions, and although we observe these differences in crystal structures there is the possibility that the movements observed may suggest a diversity of kinase conformational changes associated with regulation.

PubMed: 28993291
DOI: 10.1016/j.bbapap.2017.10.004

実験手法

X-RAY DIFFRACTION (2.5 Å)