2cdz
From Proteopedia
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| - | [[Image:2cdz.gif|left|200px]]<br /><applet load="2cdz" size=" | + | [[Image:2cdz.gif|left|200px]]<br /><applet load="2cdz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2cdz, resolution 2.30Å" /> | caption="2cdz, resolution 2.30Å" /> | ||
'''CRYSTAL STRUCTURE OF THE HUMAN P21-ACTIVATED KINASE 4 IN COMPLEX WITH CGP74514A'''<br /> | '''CRYSTAL STRUCTURE OF THE HUMAN P21-ACTIVATED KINASE 4 IN COMPLEX WITH CGP74514A'''<br /> | ||
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| + | ==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== | ==About this Structure== | ||
| - | 2CDZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4, CL and 23D as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/ | + | 2CDZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=23D:'>23D</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Known structural/functional Sites: <scene name='pdbsite=AC1:23d Binding Site For Residue A 1591'>AC1</scene>, <scene name='pdbsite=AC2:So4 Binding Site For Residue A 1592'>AC2</scene> and <scene name='pdbsite=AC3:So4 Binding Site For Residue A 1593'>AC3</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CDZ 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17292838 17292838] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| + | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Transferred entry: 2.7.11.1]] | ||
[[Category: Arrowsmith, C.]] | [[Category: Arrowsmith, C.]] | ||
[[Category: Das, S.]] | [[Category: Das, S.]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 31 10:56:37 2008'' |
Revision as of 08:56, 31 January 2008
|
CRYSTAL STRUCTURE OF THE HUMAN P21-ACTIVATED KINASE 4 IN COMPLEX WITH CGP74514A
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
2CDZ is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Known structural/functional Sites: , and . 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 Jan 31 10:56:37 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Single protein | Arrowsmith, C. | Das, S. | Debreczeni, J.E. | Delft, F.Von. | Edwards, A. | Eswaran, J. | Fedorov, O. | Filippakopoulos, P. | Knapp, S. | Sundstrom, M. | Ugochukwu, E. | Weigelt, J. | 23D | CL | SO4 | Atp-binding | Pak4 | Protein kinase | Ste20 | Transferase
