5VEE

PAK4 kinase domain in complex with FRAX486

Summary for 5VEE

• Entry DOI: 10.2210/pdb5vee/pdb
• Related: 5VED 5VEE
• Descriptor: 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)
• Functional Keywords: kinase, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 36539.14

Authors

Zhang, E.Y.,Ha, B.H.,Boggon, T.J. (deposition date: 2017-04-04, release date: 2017-10-18, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)