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[[Image:2c30.gif|left|200px]]
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{{STRUCTURE_2c30|  PDB=2c30  |  SCENE=  }}
'''CRYSTAL STRUCTURE OF THE HUMAN P21-ACTIVATED KINASE 6'''


==Crystal Structure Of The Human P21-Activated Kinase 6==
<StructureSection load='2c30' size='340' side='right'caption='[[2c30]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2c30]] is a 1 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=2C30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C30 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=2c30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c30 OCA], [https://pdbe.org/2c30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c30 RCSB], [https://www.ebi.ac.uk/pdbsum/2c30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c30 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PAK6_HUMAN PAK6_HUMAN] Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Inhibits also ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD.<ref>PMID:14573606</ref> <ref>PMID:20054820</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/c3/2c30_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=2c30 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.


==Overview==
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>
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==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2C30 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=2C30 OCA].
</div>
<div class="pdbe-citations 2c30" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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]
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[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: Berridge G]]
[[Category: Berridge, G.]]
[[Category: Bray J]]
[[Category: Bray, J.]]
[[Category: Burgess N]]
[[Category: Burgess, N.]]
[[Category: Colebrook S]]
[[Category: Colebrook, S.]]
[[Category: Das S]]
[[Category: Das, S.]]
[[Category: Edwards A]]
[[Category: Delft, F Von.]]
[[Category: Eswaran J]]
[[Category: Edwards, A.]]
[[Category: Filippakopoulos P]]
[[Category: Eswaran, J.]]
[[Category: Gileadi O]]
[[Category: Filippakopoulos, P.]]
[[Category: Knapp S]]
[[Category: Gileadi, O.]]
[[Category: Papagrigoriou E]]
[[Category: Knapp, S.]]
[[Category: Savitsky P]]
[[Category: Papagrigoriou, E.]]
[[Category: Smee C]]
[[Category: Savitsky, P.]]
[[Category: Sundstrom M]]
[[Category: Smee, C.]]
[[Category: Turnbull A]]
[[Category: Sundstrom, M.]]
[[Category: Weigelt J]]
[[Category: Turnbull, A.]]
[[Category: Von Delft F]]
[[Category: Weigelt, J.]]
[[Category: Atp-binding]]
[[Category: Crib domain]]
[[Category: Kinase]]
[[Category: Nucleotide-binding]]
[[Category: Phosphorylation]]
[[Category: Polymorphism]]
[[Category: Serine-threonine protein kinase]]
[[Category: Ste20-like]]
[[Category: Transferase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 21:10:17 2008''

Latest revision as of 10:48, 23 October 2024

Crystal Structure Of The Human P21-Activated Kinase 6Crystal Structure Of The Human P21-Activated Kinase 6

Structural highlights

2c30 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.6Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PAK6_HUMAN Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Inhibits also ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD.[1] [2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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 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[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Schrantz N, da Silva Correia J, Fowler B, Ge Q, Sun Z, Bokoch GM. Mechanism of p21-activated kinase 6-mediated inhibition of androgen receptor signaling. J Biol Chem. 2004 Jan 16;279(3):1922-31. Epub 2003 Oct 22. PMID:14573606 doi:10.1074/jbc.M311145200
  2. ↑ Zhang M, Siedow M, Saia G, Chakravarti A. Inhibition of p21-activated kinase 6 (PAK6) increases radiosensitivity of prostate cancer cells. Prostate. 2010 Jun 1;70(8):807-16. doi: 10.1002/pros.21114. PMID:20054820 doi:10.1002/pros.21114
  3. ↑ Eswaran J, Lee WH, Debreczeni JE, Filippakopoulos P, Turnbull A, Fedorov O, Deacon SW, Peterson JR, Knapp S. Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs. Structure. 2007 Feb;15(2):201-13. PMID:17292838 doi:10.1016/j.str.2007.01.001

2c30, resolution 1.60Å

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