2CDZ

CRYSTAL STRUCTURE OF THE HUMAN P21-ACTIVATED KINASE 4 IN COMPLEX WITH CGP74514A

Summary for 2CDZ

• Entry DOI: 10.2210/pdb2cdz/pdb
• Related: 2BVA
• Descriptor: SERINE/THREONINE-PROTEIN KINASE PAK 4, N2-[(1R,2S)-2-AMINOCYCLOHEXYL]-N6-(3-CHLOROPHENYL)-9-ETHYL-9H-PURINE-2,6-DIAMINE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: transferase, protein kinase, ste20, pak4, atp-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : O96013
• Total number of polymer chains: 1
• Total formula weight: 34849.16

Authors

Debreczeni, J.E.,Ugochukwu, E.,Eswaran, J.,Filippakopoulos, P.,Das, S.,Fedorov, O.,Sundstrom, M.,Arrowsmith, C.,Weigelt, J.,Edwards, A.,von Delft, F.,Knapp, S. (deposition date: 2006-01-31, release date: 2006-02-08, Last modification date: 2024-11-06)

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-, 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 (2.3 Å)