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[[ | ==HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH ALLOSTERIC ACTIVATOR PS171 BOUND TO THE PIF-POCKET== | ||
<StructureSection load='4a07' size='340' side='right' caption='[[4a07]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4a07]] 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=4A07 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A07 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=AZ7:(3S)-3-(4-CHLOROPHENYL)-4-(5,7-DICHLORO-1H-BENZIMIDAZOL-2-YL)BUTANOIC+ACID'>AZ7</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1h1w|1h1w]], [[1uu3|1uu3]], [[1w1g|1w1g]], [[1w1h|1w1h]], [[2biy|2biy]], [[1uu8|1uu8]], [[1oky|1oky]], [[1uu9|1uu9]], [[1z5m|1z5m]], [[1okz|1okz]], [[1w1d|1w1d]], [[2xch|2xch]], [[2vki|2vki]], [[2xck|2xck]], [[1uu7|1uu7]], [[1uvr|1uvr]], [[4a06|4a06]]</td></tr> | |||
<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4a07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a07 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a07 RCSB], [http://www.ebi.ac.uk/pdbsum/4a07 PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein kinases are key mediators of cellular signaling, and therefore, their activities are tightly controlled. AGC kinases are regulated by phosphorylation and by N- and C-terminal regions. Here, we studied the molecular mechanism of inhibition of atypical PKCzeta and found that the inhibition by the N-terminal region cannot be explained by a simple pseudosubstrate inhibitory mechanism. Notably, we found that the C1 domain allosterically inhibits PKCzeta activity and verified an allosteric communication between the PIF-pocket of atypical PKCs and the binding site of the C1 domain. Finally, we developed low-molecular-weight compounds that bind to the PIF-pocket and allosterically inhibit PKCzeta activity. This work establishes a central role for the PIF-pocket on the regulation of PKCzeta and allows us to envisage development of drugs targeting the PIF-pocket that can either activate or inhibit AGC kinases. | |||
Allosteric Regulation of Protein Kinase PKCzeta by the N-Terminal C1 Domain and Small Compounds to the PIF-Pocket.,Lopez-Garcia LA, Schulze JO, Frohner W, Zhang H, Suss E, Weber N, Navratil J, Amon S, Hindie V, Zeuzem S, Jorgensen TJ, Alzari PM, Neimanis S, Engel M, Biondi RM Chem Biol. 2011 Nov 23;18(11):1463-1473. PMID:22118680<ref>PMID:22118680</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]] | ||
Revision as of 10:35, 5 June 2014
HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH ALLOSTERIC ACTIVATOR PS171 BOUND TO THE PIF-POCKETHUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH ALLOSTERIC ACTIVATOR PS171 BOUND TO THE PIF-POCKET
Structural highlights
Publication Abstract from PubMedProtein kinases are key mediators of cellular signaling, and therefore, their activities are tightly controlled. AGC kinases are regulated by phosphorylation and by N- and C-terminal regions. Here, we studied the molecular mechanism of inhibition of atypical PKCzeta and found that the inhibition by the N-terminal region cannot be explained by a simple pseudosubstrate inhibitory mechanism. Notably, we found that the C1 domain allosterically inhibits PKCzeta activity and verified an allosteric communication between the PIF-pocket of atypical PKCs and the binding site of the C1 domain. Finally, we developed low-molecular-weight compounds that bind to the PIF-pocket and allosterically inhibit PKCzeta activity. This work establishes a central role for the PIF-pocket on the regulation of PKCzeta and allows us to envisage development of drugs targeting the PIF-pocket that can either activate or inhibit AGC kinases. Allosteric Regulation of Protein Kinase PKCzeta by the N-Terminal C1 Domain and Small Compounds to the PIF-Pocket.,Lopez-Garcia LA, Schulze JO, Frohner W, Zhang H, Suss E, Weber N, Navratil J, Amon S, Hindie V, Zeuzem S, Jorgensen TJ, Alzari PM, Neimanis S, Engel M, Biondi RM Chem Biol. 2011 Nov 23;18(11):1463-1473. PMID:22118680[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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