View source for 9gix


==Structure of the human mitochondrial pyruvate carrier in the apo-state==
<StructureSection load='9gix' size='340' side='right'caption='[[9gix]], [[Resolution|resolution]] 3.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9gix]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9GIX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9GIX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.65&#8491;</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=9gix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9gix OCA], [https://pdbe.org/9gix PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9gix RCSB], [https://www.ebi.ac.uk/pdbsum/9gix PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9gix ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MPC1L_HUMAN MPC1L_HUMAN] Mediates the uptake of pyruvate into mitochondria.<ref>PMID:27317664</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The mitochondrial pyruvate carrier transports pyruvate, produced by glycolysis from sugar molecules, into the mitochondrial matrix, as a crucial transport step in eukaryotic energy metabolism. The carrier is a drug target for the treatment of cancers, diabetes mellitus, neurodegeneration, and metabolic dysfunction-associated steatotic liver disease. We have solved the structure of the human MPC1L/MPC2 heterodimer in the inward- and outward-open states by cryo-electron microscopy, revealing its alternating access rocker-switch mechanism. The carrier has a central binding site for pyruvate, which contains an essential lysine and histidine residue, important for its DeltapH-dependent transport mechanism. We have also determined the binding poses of three chemically distinct inhibitor classes, which exploit the same binding site in the outward-open state by mimicking pyruvate interactions and by using aromatic stacking interactions.

Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier.,Sichrovsky M, Lacabanne D, Ruprecht JJ, Rana JJ, Stanik K, Dionysopoulou M, Sowton AP, King MS, Jones SA, Cooper L, Hardwick SW, Paris G, Chirgadze DY, Ding S, Fearnley IM, Palmer SM, Pardon E, Steyaert J, Leone V, Forrest LR, Tavoulari S, Kunji ERS Sci Adv. 2025 Apr 18;11(16):eadw1489. doi: 10.1126/sciadv.adw1489. Epub 2025 Apr , 18. PMID:40249800<ref>PMID:40249800</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9gix" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Chirgadze DY]]
[[Category: Cooper L]]
[[Category: Ding S]]
[[Category: Dionysopoulou M]]
[[Category: Fearnley IM]]
[[Category: Forrest LR]]
[[Category: Hardwick SW]]
[[Category: Jones S]]
[[Category: King MS]]
[[Category: Kunji ERS]]
[[Category: Lacabanne D]]
[[Category: Leone V]]
[[Category: Palmer S]]
[[Category: Pardon E]]
[[Category: Paris G]]
[[Category: Rana JJ]]
[[Category: Ruprecht JJ]]
[[Category: Sichrovsky M]]
[[Category: Sowton AP]]
[[Category: Stanik K]]
[[Category: Steyaert J]]
[[Category: Tavoulari S]]