View source for 4jnk

==Lactate Dehydrogenase A in complex with inhibitor compound 22==
<StructureSection load='4jnk' size='340' side='right' caption='[[4jnk]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4jnk]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JNK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JNK FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=LAC:LACTIC+ACID'>LAC</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZHK:(2R)-2-{[5-CYANO-4-(3,4-DICHLOROPHENYL)-6-OXO-1,6-DIHYDROPYRIMIDIN-2-YL]SULFANYL}-N-(4-SULFAMOYLPHENYL)PROPANAMIDE'>ZHK</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LDHA, PIG19 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4jnk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jnk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jnk RCSB], [http://www.ebi.ac.uk/pdbsum/4jnk PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN]] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:[http://omim.org/entry/612933 612933]]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.<ref>PMID:2334430</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A novel 2-thio-6-oxo-1,6-dihydropyrimidine-containing inhibitor of human lactate dehydrogenase (LDH) was identified by high-throughput screening (IC50=8.1muM). Biochemical, surface plasmon resonance, and saturation transfer difference NMR experiments indicated that the compound specifically associated with human LDHA in a manner that required simultaneous binding of the NADH co-factor. Structural variation of the screening hit resulted in significant improvements in LDHA biochemical inhibition activity (best IC50=0.48muM). A crystal structure of an optimized compound bound to human LDHA was obtained and explained many of the observed structure-activity relationships.

Identification of substituted 2-thio-6-oxo-1,6-dihydropyrimidines as inhibitors of human lactate dehydrogenase.,Dragovich PS, Fauber BP, Corson LB, Ding CZ, Eigenbrot C, Ge H, Giannetti AM, Hunsaker T, Labadie S, Liu Y, Malek S, Pan B, Peterson D, Pitts K, Purkey HE, Sideris S, Ultsch M, Vanderporten E, Wei B, Xu Q, Yen I, Yue Q, Zhang H, Zhang X Bioorg Med Chem Lett. 2013 Jun 1;23(11):3186-94. doi: 10.1016/j.bmcl.2013.04.001., Epub 2013 Apr 10. PMID:23628333<ref>PMID:23628333</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: Homo sapiens]]
[[Category: L-lactate dehydrogenase]]
[[Category: Eigenbrot, C]]
[[Category: Ultsch, M]]
[[Category: Alpha-beta]]
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
[[Category: Pyruvate reductase and lactate dehydrogenase]]