View source for 7dbk


==Crystal structure of human LDHB in complex with NADH==
<StructureSection load='7dbk' size='340' side='right'caption='[[7dbk]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7dbk]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DBK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DBK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.802&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7dbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dbk OCA], [https://pdbe.org/7dbk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dbk RCSB], [https://www.ebi.ac.uk/pdbsum/7dbk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dbk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LDHB_HUMAN LDHB_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lactate dehydrogenase (LDH) catalyses the conversion of pyruvate to lactate and NADH to NAD(+); it has two isoforms, LDHA and LDHB. LDHA is a promising target for cancer therapy, whereas LDHB is necessary for basal autophagy and cancer cell proliferation in oxidative and glycolytic cancer cells. To the best of our knowledge, selective inhibitors for LDHB have not yet been reported. Here, we developed a high-throughput mass spectrometry screening system using an LDHB enzyme assay by detecting NADH and NAD(+). As a result, we identified a small-molecule LDHB selective inhibitor AXKO-0046, an indole derivative. This compound exhibited uncompetitive LDHB inhibition (EC50 = 42 nM). X-ray crystallography revealed that AXKO-0046 bound to the potential allosteric site away from the LDHB catalytic active site, suggesting that targeting the tetramerisation interface of the two dimers is critical for the enzymatic activity. AXKO-0046 and its derivatives can be used to validate LDHB-associated pathways in cancer metabolism.

Identification of the first highly selective inhibitor of human lactate dehydrogenase B.,Shibata S, Sogabe S, Miwa M, Fujimoto T, Takakura N, Naotsuka A, Kitamura S, Kawamoto T, Soga T Sci Rep. 2021 Nov 1;11(1):21353. doi: 10.1038/s41598-021-00820-7. PMID:34725423<ref>PMID:34725423</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7dbk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Lactate dehydrogenase 3D structures|Lactate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Miwa M]]
[[Category: Sogabe S]]