This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4ks7

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 08:49, 4 August 2016

PAK6 kinase domain in complex with PF-3758309

Structural highlights

4ks7 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	4ks8
Gene:	PAK6, PAK5 (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
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]

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.

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^[3]

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

References

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ks7"

@@ Line 1: / Line 1: @@
 ==PAK6 kinase domain in complex with PF-3758309==
 <StructureSection load='4ks7' size='340' side='right' caption='[[4ks7]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
@@ Line 8: / Line 9: @@
 <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>
+<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://pdbe.org/4ks7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ks7 RCSB], [http://www.ebi.ac.uk/pdbsum/4ks7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ks7 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ks7" style="background-color:#fffaf0;"></div>
 ==See Also==

4ks7

From Proteopedia

Revision as of 08:49, 4 August 2016

PAK6 kinase domain in complex with PF-3758309

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox