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[[Image:2f57.gif|left|200px]]


{{Structure
==Crystal Structure Of The Human P21-Activated Kinase 5==
|PDB= 2f57 |SIZE=350|CAPTION= <scene name='initialview01'>2f57</scene>, resolution 1.80&Aring;
<StructureSection load='2f57' size='340' side='right'caption='[[2f57]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene> and <scene name='pdbligand=23D:N2-[(1R,2S)-2-AMINOCYCLOHEXYL]-N6-(3-CHLOROPHENYL)-9-ETHYL-9H-PURINE-2,6-DIAMINE'>23D</scene>
<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>
|ACTIVITY= [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]  
</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>
|GENE=  
<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>
}}
<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>
</table>
== Function ==
[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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f5/2f57_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


'''Crystal Structure Of The Human P21-Activated Kinase 5'''
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>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2f57" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
 
== References ==
==About this Structure==
<references/>
2F57 is a [[Single protein]] structure of sequence from [http://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].
__TOC__
 
</StructureSection>
==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://www.ncbi.nlm.nih.gov/pubmed/17292838 17292838]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Arrowsmith C]]
[[Category: Arrowsmith, C.]]
[[Category: Bray J]]
[[Category: Bray, J.]]
[[Category: Burgess N]]
[[Category: Burgess, N.]]
[[Category: Das S]]
[[Category: Das, S.]]
[[Category: Edwards A]]
[[Category: Delft, F Von.]]
[[Category: Eswaran J]]
[[Category: Edwards, A.]]
[[Category: Fedorov O]]
[[Category: Eswaran, J.]]
[[Category: Filippakopoulos P]]
[[Category: Fedorov, O.]]
[[Category: Knapp S]]
[[Category: Filippakopoulos, P.]]
[[Category: Papagrigoriou E]]
[[Category: Knapp, S.]]
[[Category: Savitsky P]]
[[Category: Papagrigoriou, E.]]
[[Category: Smee C]]
[[Category: SGC, Structural Genomics Consortium.]]
[[Category: Sundstrom M]]
[[Category: Savitsky, P.]]
[[Category: Turnbull A]]
[[Category: Smee, C.]]
[[Category: Ugochukwu E]]
[[Category: Sundstrom, M.]]
[[Category: Weigelt J]]
[[Category: Turnbull, A.]]
[[Category: Von Delft F]]
[[Category: Ugochukwu, E.]]
[[Category: Weigelt, J.]]
[[Category: 23D]]
[[Category: TRS]]
[[Category: groupii pak]]
[[Category: kinase domain]]
[[Category: pak5]]
[[Category: sgc]]
[[Category: structural genomic]]
[[Category: structural genomics consortium]]
 
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