View source for 5zjf


==LDHA-MA==
<StructureSection load='5zjf' size='340' side='right'caption='[[5zjf]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zjf]] is a 12 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=5ZJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZJF 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]] 2.602&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9G9:5,5-[(2R,3S)-2,3-dimethylbutane-1,4-diyl]bis(2H-1,3-benzodioxole)'>9G9</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=5zjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zjf OCA], [https://pdbe.org/5zjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zjf RCSB], [https://www.ebi.ac.uk/pdbsum/5zjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zjf ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:[https://omim.org/entry/612933 612933]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.<ref>PMID:2334430</ref> 
== Function ==
[https://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lactate dehydrogenase A (LDHA) is an important enzyme responsible for cancer growth and energy metabolism in various cancers via the aerobic glycolytic pathway. Here, we report that machilin A (MA), which acts as a competitive inhibitor by blocking the nicotinamide adenine dinucleotide (NAD) binding site of LDHA, suppresses growth of cancer cells and lactate production in various cancer cell types, including colon, breast, lung, and liver cancers. Furthermore, MA markedly decreased LDHA activity, lactate production, and intracellular adenosine triphosphate (ATP) levels induced by hypoxia-induced LDHA expression in cancer cells, and significantly inhibited colony formation, leading to reduced cancer cell survival. In mouse models inoculated with murine Lewis lung carcinoma, MA significantly suppressed tumor growth as observed by a reduction of tumor volume and weight; resulting from the inhibition of LDHA activity. Subsequently, the suppression of tumor-derived lactic acid in MA-treated cancer cells resulted in decrease of neovascularization through the regulation of alternatively activated macrophages (M2) polarization in macrophages. Taken together, we suggest that the reduction of lactate by MA in cancer cells directly results in a suppression of cancer cell growth. Furthermore, macrophage polarization and activation of endothelial cells for angiogenesis were indirectly regulated preventing lactate production in MA-treated cancer cells.

Machilin A Inhibits Tumor Growth and Macrophage M2 Polarization Through the Reduction of Lactic Acid.,Chung TW, Kim EY, Han CW, Park SY, Jeong MS, Yoon D, Choi HJ, Jin L, Park MJ, Kwon YJ, Lee H, Kim KJ, Park KH, Kim S, Jang SB, Ha KT Cancers (Basel). 2019 Jul 9;11(7). pii: cancers11070963. doi:, 10.3390/cancers11070963. PMID:31324019<ref>PMID:31324019</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5zjf" 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: Han CW]]
[[Category: Jang SB]]