1wbt: Difference between revisions
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<StructureSection load='1wbt' size='340' side='right'caption='[[1wbt]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='1wbt' size='340' side='right'caption='[[1wbt]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1wbt]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1wbt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WBT FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=WBT:3-FLUORO-5-MORPHOLIN-4-YL-N-[1-(2-PYRIDIN-4-YLETHYL)-1H-INDOL-6-YL]BENZAMIDE'>WBT</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=WBT:3-FLUORO-5-MORPHOLIN-4-YL-N-[1-(2-PYRIDIN-4-YLETHYL)-1H-INDOL-6-YL]BENZAMIDE'>WBT</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a9u|1a9u]], [[1bl6|1bl6]], [[1bl7|1bl7]], [[1bmk|1bmk]], [[1di9|1di9]], [[1ian|1ian]], [[1kv1|1kv1]], [[1kv2|1kv2]], [[1m7q|1m7q]], [[1ouk|1ouk]], [[1ouy|1ouy]], [[1ove|1ove]], [[1oz1|1oz1]], [[1r39|1r39]], [[1r3c|1r3c]], [[1w7h|1w7h]], [[1w82|1w82]], [[1w83|1w83]], [[1w84|1w84]], [[1wbn|1wbn]], [[1wbo|1wbo]], [[1wbs|1wbs]], [[1wbv|1wbv]], [[1wbw|1wbw]], [[1wfc|1wfc]], [[1yqj|1yqj]], [[1zz2|1zz2]], [[1zzl|1zzl]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1a9u|1a9u]], [[1bl6|1bl6]], [[1bl7|1bl7]], [[1bmk|1bmk]], [[1di9|1di9]], [[1ian|1ian]], [[1kv1|1kv1]], [[1kv2|1kv2]], [[1m7q|1m7q]], [[1ouk|1ouk]], [[1ouy|1ouy]], [[1ove|1ove]], [[1oz1|1oz1]], [[1r39|1r39]], [[1r3c|1r3c]], [[1w7h|1w7h]], [[1w82|1w82]], [[1w83|1w83]], [[1w84|1w84]], [[1wbn|1wbn]], [[1wbo|1wbo]], [[1wbs|1wbs]], [[1wbv|1wbv]], [[1wbw|1wbw]], [[1wfc|1wfc]], [[1yqj|1yqj]], [[1zz2|1zz2]], [[1zzl|1zzl]]</div></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1wbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wbt OCA], [https://pdbe.org/1wbt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wbt RCSB], [https://www.ebi.ac.uk/pdbsum/1wbt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wbt ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
Revision as of 09:29, 6 October 2021
Identification of novel p38 alpha MAP Kinase inhibitors using fragment-based lead generation.Identification of novel p38 alpha MAP Kinase inhibitors using fragment-based lead generation.
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe describe the structure-guided optimization of the molecular fragments 2-amino-3-benzyloxypyridine 1 (IC(50) 1.3 mM) and 3-(2-(4-pyridyl)ethyl)indole 2 (IC(50) 35 microM) identified using X-ray crystallographic screening of p38alpha MAP kinase. Using two separate case studies, the article focuses on the key compounds synthesized, the structure-activity relationships and the binding mode observations made during this optimization process, resulting in two potent lead series that demonstrate significant increases in activity. We describe the process of compound elaboration either through the growing out from fragments into adjacent pockets or through the conjoining of overlapping fragments and demonstrate that we have exploited the mobile conserved activation loop, consisting in part of Asp168-Phe169-Gly170 (DFG), to generate significant improvements in potency and kinase selectivity. Identification of novel p38alpha MAP kinase inhibitors using fragment-based lead generation.,Gill AL, Frederickson M, Cleasby A, Woodhead SJ, Carr MG, Woodhead AJ, Walker MT, Congreve MS, Devine LA, Tisi D, O'Reilly M, Seavers LC, Davis DJ, Curry J, Anthony R, Padova A, Murray CW, Carr RA, Jhoti H J Med Chem. 2005 Jan 27;48(2):414-26. PMID:15658855[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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