2f57
From Proteopedia
(New page: 200px<br /> <applet load="2f57" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f57, resolution 1.80Å" /> '''Crystal Structure O...) |
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| - | [[Image:2f57.gif|left|200px]]<br /> | + | [[Image:2f57.gif|left|200px]]<br /><applet load="2f57" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2f57, resolution 1.80Å" /> | caption="2f57, resolution 1.80Å" /> | ||
'''Crystal Structure Of The Human P21-Activated Kinase 5'''<br /> | '''Crystal Structure Of The Human P21-Activated Kinase 5'''<br /> | ||
==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== | ||
| - | 2F57 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 TRS and 23D 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] Full crystallographic information is available from [http:// | + | 2F57 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=TRS:'>TRS</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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F57 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Burgess, N.]] | [[Category: Burgess, N.]] | ||
[[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: Knapp, S.]] | [[Category: Knapp, S.]] | ||
[[Category: Papagrigoriou, E.]] | [[Category: Papagrigoriou, E.]] | ||
| - | [[Category: SGC, Structural | + | [[Category: SGC, Structural Genomics Consortium.]] |
[[Category: Savitsky, P.]] | [[Category: Savitsky, P.]] | ||
[[Category: Smee, C.]] | [[Category: Smee, C.]] | ||
| Line 42: | Line 41: | ||
[[Category: structural genomics consortium]] | [[Category: structural genomics consortium]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:17:51 2008'' |
Revision as of 15:17, 21 February 2008
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Crystal Structure Of The Human P21-Activated Kinase 5
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
2F57 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 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 17:17:51 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Single protein | Arrowsmith, C. | Bray, J. | Burgess, N. | Das, S. | Delft, F Von. | Edwards, A. | Eswaran, J. | Fedorov, O. | Filippakopoulos, P. | Knapp, S. | Papagrigoriou, E. | SGC, Structural Genomics Consortium. | Savitsky, P. | Smee, C. | Sundstrom, M. | Turnbull, A. | Ugochukwu, E. | Weigelt, J. | 23D | TRS | Groupii paks | Kinase domains | Pak5 | Sgc | Structural genomics | Structural genomics consortium
