View source for 6kdy


==Crystal structure of the alpha bata heterodimer of human IDH3 in complex with NAD.==
<StructureSection load='6kdy' size='340' side='right'caption='[[6kdy]], [[Resolution|resolution]] 3.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6kdy]] 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=6KDY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KDY 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]] 3.02&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PE7:1-DEOXY-1-THIO-HEPTAETHYLENE+GLYCOL'>PE7</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=6kdy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kdy OCA], [https://pdbe.org/6kdy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kdy RCSB], [https://www.ebi.ac.uk/pdbsum/6kdy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kdy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IDH3A_HUMAN IDH3A_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mammalian mitochondrial NAD-dependent isocitrate dehydrogenase (NAD-IDH) catalyzes the decarboxylation of isocitrate into alpha-ketoglutarate in the tricarboxylic acid cycle. It exists as the alpha2betagamma heterotetramer composed of the alphabeta and alphagamma heterodimers. Different from the alphagamma heterodimer that can be allosterically activated by CIT and ADP, the alphabeta heterodimer cannot be allosterically regulated by the activators; however, the molecular mechanism is unclear. We report here the crystal structures of the alphabeta heterodimer of human NAD-IDH with the alpha subunit in apo form and in Ca(2+)-bound, NAD-bound, and NADH-bound forms. Structural analyses and comparisons reveal that the alphabeta heterodimer has a similar yet more compact overall structure compared with the alphagamma heterodimer and contains a pseudo-allosteric site that is structurally different from the allosteric site. In particular, the beta3-alpha3 and beta12-alpha8 loops of the beta subunit at the pseudo-allosteric site adopt significantly different conformations from those of the gamma subunit at the allosteric site and hence impede the binding of the activators, explaining why the alphabeta heterodimer cannot be allosterically regulated by the activators. The structural data also show that NADH can compete with NAD to bind to the active site and inhibits the activity of the alphabeta heterodimer. These findings together with the biochemical data reveal the molecular basis for the function of the alphabeta heterodimer of human NAD-IDH.

Molecular basis for the function of the alphabeta heterodimer of human NAD-dependent isocitrate dehydrogenase.,Sun P, Ma T, Zhang T, Zhu H, Zhang J, Liu Y, Ding J J Biol Chem. 2019 Nov 1;294(44):16214-16227. doi: 10.1074/jbc.RA119.010099. Epub , 2019 Sep 12. PMID:31515270<ref>PMID:31515270</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6kdy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Isocitrate dehydrogenase 3D structures|Isocitrate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ding J]]
[[Category: Sun P]]