4aw0: Difference between revisions
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[[ | ==Human PDK1 Kinase Domain in Complex with Allosteric Compound PS182 Bound to the PIF-Pocket== | ||
<StructureSection load='4aw0' size='340' side='right' caption='[[4aw0]], [[Resolution|resolution]] 1.43Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4aw0]] is a 1 chain structure with 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=4AW0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AW0 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTD:DITHIANE+DIOL'>DTD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MJF:[(1R)-3-(4-CHLOROPHENYL)-3-OXO-1-PHENYLPROPYL]PROPANEDIOIC+ACID'>MJF</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1h1w|1h1w]], [[1oky|1oky]], [[1okz|1okz]], [[1uu3|1uu3]], [[1uu7|1uu7]], [[1uu8|1uu8]], [[1uu9|1uu9]], [[1uvr|1uvr]], [[1w1d|1w1d]], [[1w1g|1w1g]], [[1w1h|1w1h]], [[1z5m|1z5m]], [[2biy|2biy]], [[2vki|2vki]], [[2xch|2xch]], [[2xck|2xck]], [[4a06|4a06]], [[4a07|4a07]], [[4aw1|4aw1]]</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=4aw0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aw0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4aw0 RCSB], [http://www.ebi.ac.uk/pdbsum/4aw0 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The PIF-pocket of AGC protein kinases participates in the physiologic mechanism of regulation by acting as a docking site for substrates and as a switch for the transduction of the conformational changes needed for activation or inhibition. We describe the effects of compounds that bind to the PIF-pocket of PDK1. In vitro, PS210 is a potent activator of PDK1, and the crystal structure of the PDK1-ATP-PS210 complex shows that PS210 stimulates the closure of the kinase domain. However, in cells, the prodrug of PS210 (PS423) acts as a substrate-selective inhibitor of PDK1, inhibiting the phosphorylation and activation of S6K, which requires docking to the PIF-pocket, but not affecting PKB/Akt. This work describes a tool to study the dynamics of PDK1 activity and a potential approach for drug discovery. | |||
Substrate-Selective Inhibition of Protein Kinase PDK1 by Small Compounds that Bind to the PIF-Pocket Allosteric Docking Site.,Busschots K, Lopez-Garcia LA, Lammi C, Stroba A, Zeuzem S, Piiper A, Alzari PM, Neimanis S, Arencibia JM, Engel M, Schulze JO, Biondi RM Chem Biol. 2012 Sep 21;19(9):1152-63. doi: 10.1016/j.chembiol.2012.07.017. PMID:22999883<ref>PMID:22999883</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | |||
*[[3-phosphoinositide-dependent protein kinase 1|3-phosphoinositide-dependent protein kinase 1]] | |||
== | == References == | ||
[[ | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Alzari, P M | [[Category: Alzari, P M]] | ||
[[Category: Arencibia, J M | [[Category: Arencibia, J M]] | ||
[[Category: Biondi, R M | [[Category: Biondi, R M]] | ||
[[Category: Busschots, K | [[Category: Busschots, K]] | ||
[[Category: Engel, M | [[Category: Engel, M]] | ||
[[Category: Lammi, C | [[Category: Lammi, C]] | ||
[[Category: Lopez-Garcia, L A | [[Category: Lopez-Garcia, L A]] | ||
[[Category: Neimanis, S | [[Category: Neimanis, S]] | ||
[[Category: Piiper, A | [[Category: Piiper, A]] | ||
[[Category: Schulze, J O | [[Category: Schulze, J O]] | ||
[[Category: Stroba, A | [[Category: Stroba, A]] | ||
[[Category: Zeuzem, S | [[Category: Zeuzem, S]] | ||
[[Category: Agc protein kinase]] | [[Category: Agc protein kinase]] | ||
[[Category: Allosteric regulation]] | [[Category: Allosteric regulation]] | ||
Revision as of 17:50, 9 December 2014
Human PDK1 Kinase Domain in Complex with Allosteric Compound PS182 Bound to the PIF-Pocket
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