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''' | ==Human PDK1-PKCzeta Kinase Chimera in Complex with Allosteric Compound PS315 Bound to the PIF-Pocket== | ||
<StructureSection load='4ct1' size='340' side='right' caption='[[4ct1]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ct1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CT1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CT1 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=31S:(2Z)-3-(BIPHENYL-4-YL)-5-(4-CHLOROPHENYL)PENT-2-ENOIC+ACID'>31S</scene>, <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><br> | |||
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ct2|4ct2]]</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=4ct1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ct1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ct1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ct1 PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein kinases play important regulatory roles in cells and organisms. Therefore, they are subject to specific and tight mechanisms of regulation that ultimately converge on the catalytic domain and allow the kinases to be activated or inhibited only upon the appropriate stimuli. AGC protein kinases have a pocket in the catalytic domain, the PDK1-interacting fragment (PIF)-pocket, which is a key mediator of the activation. We show here that helix alphaC within the PIF-pocket of atypical protein kinase C (aPKC) is the target of the interaction with its inhibitory N-terminal domains. We also provide structural evidence that the small compound PS315 is an allosteric inhibitor that binds to the PIF-pocket of aPKC. PS315 exploits the physiological dynamics of helix alphaC for its binding and allosteric inhibition. The results will support research on allosteric mechanisms and selective drug development efforts against PKC isoforms. | |||
Molecular Mechanism of Regulation of the Atypical Protein Kinase C by N-terminal Domains and an Allosteric Small Compound.,Zhang H, Neimanis S, Lopez-Garcia LA, Arencibia JM, Amon S, Stroba A, Zeuzem S, Proschak E, Stark H, Bauer AF, Busschots K, Jorgensen TJ, Engel M, Schulze JO, Biondi RM Chem Biol. 2014 May 14. pii: S1074-5521(14)00145-8. doi:, 10.1016/j.chembiol.2014.04.007. PMID:24836908<ref>PMID:24836908</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Non-specific serine/threonine protein kinase]] | |||
[[Category: Biondi, R M.]] | |||
[[Category: Lopez-Garcia, L A.]] | |||
[[Category: Schulze, J O.]] | |||
[[Category: Zhang, H.]] | |||
[[Category: Agc protein kinase]] | |||
[[Category: Allosteric regulation]] | |||
[[Category: Allosteric site]] | |||
[[Category: Chimeric protein]] | |||
[[Category: Phosphorylation]] | |||
[[Category: Transferase]] | |||
Revision as of 12:43, 28 May 2014
Human PDK1-PKCzeta Kinase Chimera in Complex with Allosteric Compound PS315 Bound to the PIF-PocketHuman PDK1-PKCzeta Kinase Chimera in Complex with Allosteric Compound PS315 Bound to the PIF-Pocket
Structural highlights
Publication Abstract from PubMedProtein kinases play important regulatory roles in cells and organisms. Therefore, they are subject to specific and tight mechanisms of regulation that ultimately converge on the catalytic domain and allow the kinases to be activated or inhibited only upon the appropriate stimuli. AGC protein kinases have a pocket in the catalytic domain, the PDK1-interacting fragment (PIF)-pocket, which is a key mediator of the activation. We show here that helix alphaC within the PIF-pocket of atypical protein kinase C (aPKC) is the target of the interaction with its inhibitory N-terminal domains. We also provide structural evidence that the small compound PS315 is an allosteric inhibitor that binds to the PIF-pocket of aPKC. PS315 exploits the physiological dynamics of helix alphaC for its binding and allosteric inhibition. The results will support research on allosteric mechanisms and selective drug development efforts against PKC isoforms. Molecular Mechanism of Regulation of the Atypical Protein Kinase C by N-terminal Domains and an Allosteric Small Compound.,Zhang H, Neimanis S, Lopez-Garcia LA, Arencibia JM, Amon S, Stroba A, Zeuzem S, Proschak E, Stark H, Bauer AF, Busschots K, Jorgensen TJ, Engel M, Schulze JO, Biondi RM Chem Biol. 2014 May 14. pii: S1074-5521(14)00145-8. doi:, 10.1016/j.chembiol.2014.04.007. PMID:24836908[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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