View source for 4aj2

==rat LDHA in complex with 5-(2-chlorophenyl)-1H-tetrazole==
<StructureSection load='4aj2' size='340' side='right' caption='[[4aj2]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4aj2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AJ2 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=52C:5-(2-CHLOROPHENYL)-1H-TETRAZOLE'>52C</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]], [[4aj4|4aj4]], [[4aje|4aje]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4aj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aj2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4aj2 RCSB], [http://www.ebi.ac.uk/pdbsum/4aj2 PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lactate 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<ref>PMID:22417091</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>

==See Also==
*[[Lactate Dehydrogenase|Lactate Dehydrogenase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: L-lactate dehydrogenase]]
[[Category: Rattus norvegicus]]
[[Category: Brassington, C]]
[[Category: Davies, G]]
[[Category: Frazer, M]]
[[Category: Hassall, G]]
[[Category: Tart, J]]
[[Category: Tucker, J A]]
[[Category: Vogtherr, M]]
[[Category: Ward, R]]
[[Category: Fragment-based lead generated inhibitor]]
[[Category: Oxidoreductase-inhibitor complex]]