5vxo: Difference between revisions
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New page: '''Unreleased structure''' The entry 5vxo is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures |
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==Crystal Structure Analysis of human CLYBL in complex with propionyl-CoA== | |||
<StructureSection load='5vxo' size='340' side='right'caption='[[5vxo]], [[Resolution|resolution]] 2.27Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5vxo]] is a 3 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=5VXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VXO 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]] 2.266Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1VU:PROPIONYL+COENZYME+A'>1VU</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5vxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vxo OCA], [https://pdbe.org/5vxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vxo RCSB], [https://www.ebi.ac.uk/pdbsum/5vxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vxo ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CLYBL_HUMAN CLYBL_HUMAN] Mitochondrial malate and beta-methylmalate synthase, which may be involved in vitamin B12 metabolism (Probable). Acts both as a malate synthase, converting glyoxylate and acetyl-CoA to malate. Also acts as a beta-methylmalate synthase by mediating conversion of glyoxylate and propionyl-CoA to beta-methylmalate (PubMed:24334609).<ref>PMID:24334609</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
CLYBL encodes a ubiquitously expressed mitochondrial enzyme, conserved across all vertebrates, whose cellular activity and pathway assignment are unknown. Its homozygous loss is tolerated in seemingly healthy individuals, with reduced circulating B12 levels being the only and consistent phenotype reported to date. Here, by combining enzymology, structural biology, and activity-based metabolomics, we report that CLYBL operates as a citramalyl-CoA lyase in mammalian cells. Cells lacking CLYBL accumulate citramalyl-CoA, an intermediate in the C5-dicarboxylate metabolic pathway that includes itaconate, a recently identified human anti-microbial metabolite and immunomodulator. We report that CLYBL loss leads to a cell-autonomous defect in the mitochondrial B12 metabolism and that itaconyl-CoA is a cofactor-inactivating, substrate-analog inhibitor of the mitochondrial B12-dependent methylmalonyl-CoA mutase (MUT). Our work de-orphans the function of human CLYBL and reveals that a consequence of exposure to the immunomodulatory metabolite itaconate is B12 inactivation. | |||
The Human Knockout Gene CLYBL Connects Itaconate to Vitamin B12.,Shen H, Campanello GC, Flicker D, Grabarek Z, Hu J, Luo C, Banerjee R, Mootha VK Cell. 2017 Nov 2;171(4):771-782.e11. doi: 10.1016/j.cell.2017.09.051. Epub 2017, Oct 19. PMID:29056341<ref>PMID:29056341</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5vxo" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Shen H]] | |||
Latest revision as of 14:01, 4 October 2023
Crystal Structure Analysis of human CLYBL in complex with propionyl-CoA
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