4ajh: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='4ajh' size='340' side='right'caption='[[4ajh]], [[Resolution|resolution]] 1.93Å' scene=''> | <StructureSection load='4ajh' size='340' side='right'caption='[[4ajh]], [[Resolution|resolution]] 1.93Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ajh]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4ajh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AJH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2B4:2-(4-BROMANYLPHENOXY)PROPANEDIOIC+ACID'>2B4</scene>, <scene name='pdbligand=88S:N-(2-METHYL-1,3-BENZOTHIAZOL-6-YL)-3-UREIDO-PROPANAMIDE'>88S</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2B4:2-(4-BROMANYLPHENOXY)PROPANEDIOIC+ACID'>2B4</scene>, <scene name='pdbligand=88S:N-(2-METHYL-1,3-BENZOTHIAZOL-6-YL)-3-UREIDO-PROPANAMIDE'>88S</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4aj1|4aj1]], [[4aj2|4aj2]], [[4aj4|4aj4]], [[4aje|4aje]], [[4aji|4aji]], [[4ajj|4ajj]], [[4ajk|4ajk]], [[4ajl|4ajl]], [[4ajn|4ajn]], [[4ajo|4ajo]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4aj1|4aj1]], [[4aj2|4aj2]], [[4aj4|4aj4]], [[4aje|4aje]], [[4aji|4aji]], [[4ajj|4ajj]], [[4ajk|4ajk]], [[4ajl|4ajl]], [[4ajn|4ajn]], [[4ajo|4ajo]]</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/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27] </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=4ajh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ajh OCA], [https://pdbe.org/4ajh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ajh RCSB], [https://www.ebi.ac.uk/pdbsum/4ajh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ajh ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
Revision as of 08:36, 25 August 2022
rat LDHA in complex with N-(2-methyl-1,3-benzothiazol-6-yl)-3-ureido- propanamide and 2-(4-bromophenoxy)propanedioic acidrat LDHA in complex with N-(2-methyl-1,3-benzothiazol-6-yl)-3-ureido- propanamide and 2-(4-bromophenoxy)propanedioic acid
Structural highlights
Publication Abstract from PubMedLactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work. Design and synthesis of novel lactate dehydrogenase a inhibitors by fragment-based lead generation.,Ward RA, Brassington C, Breeze AL, Caputo A, Critchlow S, Davies G, Goodwin L, Hassall G, Greenwood R, Holdgate GA, Mrosek M, Norman RA, Pearson S, Tart J, Tucker JA, Vogtherr M, Whittaker D, Wingfield J, Winter J, Hudson K J Med Chem. 2012 Apr 12;55(7):3285-306. Epub 2012 Mar 26. PMID:22417091[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||