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[[ | ==P38 inhibitor-bound== | ||
<StructureSection load='3p5k' size='340' side='right' caption='[[3p5k]], [[Resolution|resolution]] 2.09Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3p5k]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P5K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P5K FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=P5K:1-{5-TERT-BUTYL-3-[(1,1-DIOXIDOTHIOMORPHOLIN-4-YL)CARBONYL]THIOPHEN-2-YL}-3-NAPHTHALEN-1-YLUREA'>P5K</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3p78|3p78]], [[3p79|3p79]], [[3p7a|3p7a]], [[3p7b|3p7b]], [[3p7c|3p7c]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mapk14, Crk1, Csbp1, Csbp2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=3p5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p5k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p5k RCSB], [http://www.ebi.ac.uk/pdbsum/3p5k PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Discovery of a new class of DFG-out p38alpha kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the alphaC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38alpha IC(50)=22nM) and highly selective (>/=150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor. | |||
Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD).,Moffett K, Konteatis Z, Nguyen D, Shetty R, Ludington J, Fujimoto T, Lee KJ, Chai X, Namboodiri H, Karpusas M, Dorsey B, Guarnieri F, Bukhtiyarova M, Springman E, Michelotti E Bioorg Med Chem Lett. 2011 Sep 28. PMID:22014550<ref>PMID:22014550</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]] | *[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Mitogen-activated protein kinase]] | [[Category: Mitogen-activated protein kinase]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Namboodiri, H | [[Category: Namboodiri, H]] | ||
[[Category: Kinase]] | [[Category: Kinase]] | ||
[[Category: Transferase-transferase inhibitor complex]] | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 15:29, 9 December 2014
P38 inhibitor-boundP38 inhibitor-bound
Structural highlights
Publication Abstract from PubMedDiscovery of a new class of DFG-out p38alpha kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the alphaC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38alpha IC(50)=22nM) and highly selective (>/=150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor. Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD).,Moffett K, Konteatis Z, Nguyen D, Shetty R, Ludington J, Fujimoto T, Lee KJ, Chai X, Namboodiri H, Karpusas M, Dorsey B, Guarnieri F, Bukhtiyarova M, Springman E, Michelotti E Bioorg Med Chem Lett. 2011 Sep 28. PMID:22014550[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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