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{{STRUCTURE_4ks7| PDB=4ks7 | SCENE= }}
==PAK6 kinase domain in complex with PF-3758309==
===PAK6 kinase domain in complex with PF-3758309===
<StructureSection load='4ks7' size='340' side='right' caption='[[4ks7]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
{{ABSTRACT_PUBMED_24204982}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4ks7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KS7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KS7 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=X4Z:(3E)-N-[(1S)-2-(DIMETHYLAMINO)-1-PHENYLETHYL]-6,6-DIMETHYL-3-[(2-METHYLTHIENO[3,2-D]PYRIMIDIN-4-YL)IMINO]-4,6-DIHYDROPYRROLO[3,4-C]PYRAZOLE-5(3H)-CARBOXAMIDE'>X4Z</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ks8|4ks8]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PAK6, PAK5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ks7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ks7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ks7 RCSB], [http://www.ebi.ac.uk/pdbsum/4ks7 PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The p21-activated kinases (PAKs) are important effectors of Rho-family small GTPases. The PAK family consists of two groups, type I and type II, which have different modes of regulation and signaling. PAK6, a type II PAK, influences behavior and locomotor function in mice and has an ascribed role in androgen receptor signaling. Here we show that PAK6 has a peptide substrate specificity very similar to the other type II PAKs, PAK4 and PAK5 (PAK7). We find that PAK6 catalytic activity is inhibited by a peptide corresponding to its N-terminal pseudosubstrate. Introduction of a melanoma-associated mutation, P52L, into this peptide reduces pseudosubstrate autoinhibition of PAK6, and increases phosphorylation of its substrate PACSIN1 (Syndapin I) in cells. Finally we determine two co-crystal structures of PAK6 catalytic domain in complex with ATP-competitive inhibitors. We determined the 1.4 A co-crystal structure of PAK6 with the type II PAK inhibitor PF-3758309, and the 1.95 A co-crystal structure of PAK6 with sunitinib. These findings provide new insights into the structure-function relationships of PAK6 and may facilitate development of PAK6 targeted therapies.


==Function==
Substrate and Inhibitor Specificity of the Type II p21-Activated Kinase, PAK6.,Gao J, Ha BH, Lou HJ, Morse EM, Zhang R, Calderwood DA, Turk BE, Boggon TJ PLoS One. 2013 Oct 28;8(10):e77818. doi: 10.1371/journal.pone.0077818. PMID:24204982<ref>PMID:24204982</ref>
[[http://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>


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4ks7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KS7 OCA].
</div>


==Reference==
==See Also==
<ref group="xtra">PMID:024204982</ref><references group="xtra"/><references/>
*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Human]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Boggon, T J.]]
[[Category: Boggon, T J]]
[[Category: Gao, J.]]
[[Category: Gao, J]]
[[Category: Phosphorylation]]
[[Category: Phosphorylation]]
[[Category: Phosphotransfer]]
[[Category: Phosphotransfer]]
[[Category: Protein kinase]]
[[Category: Protein kinase]]
[[Category: Transferase-transferase inhibitor complex]]
[[Category: Transferase-transferase inhibitor complex]]
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