2c30
From Proteopedia
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==Overview== | ==Overview== | ||
| - | p21-activated kinases have been classified into two groups based on their | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Transferred entry: 2 | + | [[Category: Transferred entry: 2 7.11 1]] |
[[Category: Arrowsmith, C.]] | [[Category: Arrowsmith, C.]] | ||
[[Category: Berridge, G.]] | [[Category: Berridge, G.]] | ||
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[[Category: Colebrook, S.]] | [[Category: Colebrook, S.]] | ||
[[Category: Das, S.]] | [[Category: Das, S.]] | ||
| - | [[Category: Delft, F | + | [[Category: Delft, F Von.]] |
[[Category: Edwards, A.]] | [[Category: Edwards, A.]] | ||
[[Category: Eswaran, J.]] | [[Category: Eswaran, J.]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:44:20 2008'' |
Revision as of 14:44, 21 February 2008
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CRYSTAL STRUCTURE OF THE HUMAN P21-ACTIVATED KINASE 6
Overview
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.
About this Structure
2C30 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs., Eswaran J, Lee WH, Debreczeni JE, Filippakopoulos P, Turnbull A, Fedorov O, Deacon SW, Peterson JR, Knapp S, Structure. 2007 Feb;15(2):201-13. PMID:17292838
Page seeded by OCA on Thu Feb 21 16:44:20 2008
Categories: Homo sapiens | Single protein | Transferred entry: 2 7.11 1 | Arrowsmith, C. | Berridge, G. | Bray, J. | Burgess, N. | Colebrook, S. | Das, S. | Delft, F Von. | Edwards, A. | Eswaran, J. | Filippakopoulos, P. | Gileadi, O. | Knapp, S. | Papagrigoriou, E. | Savitsky, P. | Smee, C. | Sundstrom, M. | Turnbull, A. | Weigelt, J. | CL | PO4 | Atp-binding | Crib domain | Kinase | Nucleotide-binding | Phosphorylation | Polymorphism | Serine-threonine protein kinase | Ste20-like | Transferase
