2C30
Crystal Structure Of The Human P21-Activated Kinase 6
Summary for 2C30
| Entry DOI | 10.2210/pdb2c30/pdb |
| Descriptor | SERINE/THREONINE-PROTEIN KINASE PAK 6, PHOSPHATE ION, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | crib domain, atp-binding, transferase, nucleotide-binding |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 36809.69 |
| Authors | Filippakopoulos, P.,Berridge, G.,Bray, J.,Burgess, N.,Colebrook, S.,Das, S.,Eswaran, J.,Gileadi, O.,Papagrigoriou, E.,Savitsky, P.,Smee, C.,Turnbull, A.,Sundstrom, M.,Arrowsmith, C.,Weigelt, J.,Edwards, A.,von Delft, F.,Knapp, S. (deposition date: 2005-10-02, release date: 2006-02-08, Last modification date: 2024-10-23) |
| 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 Cited by 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: 17292838DOI: 10.1016/J.STR.2007.01.001 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
Download full validation report
