2F57

Crystal Structure Of The Human P21-Activated Kinase 5

Summary for 2F57

• Entry DOI: 10.2210/pdb2f57/pdb
• Descriptor: Serine/threonine-protein kinase PAK 7, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, N2-[(1R,2S)-2-AMINOCYCLOHEXYL]-N6-(3-CHLOROPHENYL)-9-ETHYL-9H-PURINE-2,6-DIAMINE, ... (4 entities in total)
• Functional Keywords: pak5, kinase domains, groupii paks, structural genomics, structural genomics consortium, sgc, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion: Q9P286
• Total number of polymer chains: 2
• Total formula weight: 73127.64

Authors

Eswaran, J.,Turnbull, A.,Ugochukwu, E.,Papagrigoriou, E.,Bray, J.,Das, S.,Savitsky, P.,Smee, C.,Burgess, N.,Fedorov, O.,Filippakopoulos, P.,von Delft, F.,Arrowsmith, C.,Weigelt, J.,Sundstrom, M.,Edwards, A.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2005-11-25, release date: 2005-12-13, Last modification date: 2024-11-20)

Primary citation

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, 15:201-213, 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

Experimental method

X-RAY DIFFRACTION (1.8 Å)