2f57

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[[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 1.80&Aring;" />
 
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'''Crystal Structure Of The Human P21-Activated Kinase 5'''<br />
 
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==Overview==
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==Crystal Structure Of The Human P21-Activated Kinase 5==
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<StructureSection load='2f57' size='340' side='right'caption='[[2f57]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2f57]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F57 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F57 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=23D:N2-[(1R,2S)-2-AMINOCYCLOHEXYL]-N6-(3-CHLOROPHENYL)-9-ETHYL-9H-PURINE-2,6-DIAMINE'>23D</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2f57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f57 OCA], [https://pdbe.org/2f57 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f57 RCSB], [https://www.ebi.ac.uk/pdbsum/2f57 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f57 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PAK5_HUMAN PAK5_HUMAN] Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates the proto-oncogene RAF1 and stimulates its kinase activity. Promotes cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Phosphorylates CTNND1, probably to regulate cytoskeletal organization and cell morphology. Keeps microtubules stable through MARK2 inhibition and destabilizes the F-actin network leading to the disappearance of stress fibers and focal adhesions.<ref>PMID:12897128</ref> <ref>PMID:16014608</ref> <ref>PMID:16581795</ref> <ref>PMID:18465753</ref> <ref>PMID:20564219</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f5/2f57_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2f57 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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.
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.
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==About this Structure==
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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<ref>PMID:17292838</ref>
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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].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2f57" style="background-color:#fffaf0;"></div>
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Single protein]]
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[[Category: Arrowsmith, C.]]
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[[Category: Bray, J.]]
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[[Category: Burgess, N.]]
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[[Category: Das, S.]]
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[[Category: Delft, F Von.]]
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[[Category: Edwards, A.]]
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[[Category: Eswaran, J.]]
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[[Category: Fedorov, O.]]
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[[Category: Filippakopoulos, P.]]
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[[Category: Knapp, S.]]
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[[Category: Papagrigoriou, E.]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Savitsky, P.]]
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[[Category: Smee, C.]]
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[[Category: Sundstrom, M.]]
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[[Category: Turnbull, A.]]
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[[Category: Ugochukwu, E.]]
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[[Category: Weigelt, J.]]
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[[Category: 23D]]
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[[Category: TRS]]
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[[Category: groupii paks ]]
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[[Category: kinase domains]]
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[[Category: pak5]]
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[[Category: sgc]]
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[[Category: structural genomics]]
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[[Category: structural genomics consortium]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:17:51 2008''
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==See Also==
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Arrowsmith C]]
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[[Category: Bray J]]
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[[Category: Burgess N]]
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[[Category: Das S]]
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[[Category: Edwards A]]
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[[Category: Eswaran J]]
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[[Category: Fedorov O]]
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[[Category: Filippakopoulos P]]
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[[Category: Knapp S]]
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[[Category: Papagrigoriou E]]
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[[Category: Savitsky P]]
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[[Category: Smee C]]
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[[Category: Sundstrom M]]
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[[Category: Turnbull A]]
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[[Category: Ugochukwu E]]
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[[Category: Weigelt J]]
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[[Category: Von Delft F]]

Current revision

Crystal Structure Of The Human P21-Activated Kinase 5

PDB ID 2f57

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