View source for 6vp0


==Human Diacylglycerol Acyltransferase 1 in complex with oleoyl-CoA==
<StructureSection load='6vp0' size='340' side='right'caption='[[6vp0]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vp0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VP0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3VV:S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-4-HYDROXY-3-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]-3,5,9-TRIHYDROXY-8,8-DIMETHYL-3,5-DIOXIDO-10,14-DIOXO-2,4,6-TRIOXA-11,15-DIAZA-3LAMBDA~5~,5LAMBDA~5~-DIPHOSPHAHEPTADECAN-17-YL}+(9Z)-OCTADEC-9-ENETHIOATE+(NON-PREFERRED+NAME)'>3VV</scene>, <scene name='pdbligand=AV0:2-decyl-2-{[(4-O-alpha-D-glucopyranosyl-beta-D-glucopyranosyl)oxy]methyl}dodecyl+4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside'>AV0</scene>, <scene name='pdbligand=P5S:O-[(R)-{[(2R)-2,3-BIS(OCTADECANOYLOXY)PROPYL]OXY}(HYDROXY)PHOSPHORYL]-L-SERINE'>P5S</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DGAT1, AGRP1, DGAT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6vp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vp0 OCA], [https://pdbe.org/6vp0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vp0 RCSB], [https://www.ebi.ac.uk/pdbsum/6vp0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vp0 ProSAT]</span></td></tr>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/DGAT1_HUMAN DGAT1_HUMAN]] Congenital chronic diarrhea with protein-losing enteropathy. The disease is caused by mutations affecting the gene represented in this entry. 
== Function ==
[[https://www.uniprot.org/uniprot/DGAT1_HUMAN DGAT1_HUMAN]] Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. In contrast to DGAT2 it is not essential for survival. May be involved in VLDL (very low density lipoprotein) assembly. In liver, plays a role in esterifying exogenous fatty acids to glycerol. Functions as the major acyl-CoA retinol acyltransferase (ARAT) in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity leading to skin and hair disorders.<ref>PMID:16214399</ref> <ref>PMID:9756920</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Diacylglycerol O-acyltransferase 1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans(1). DGAT1 belongs to the membrane-bound O-acyltransferase (MBOAT) superfamily, members of which are found in all kingdoms of life and are involved in the acylation of lipids and proteins(2,3). How human DGAT1 and other mammalian members of the MBOAT family recognize their substrates and catalyse their reactions is unknown. The absence of three-dimensional structures also hampers rational targeting of DGAT1 for therapeutic purposes. Here we present the cryo-electron microscopy structure of human DGAT1 in complex with an oleoyl-CoA substrate. Each DGAT1 protomer has nine transmembrane helices, eight of which form a conserved structural fold that we name the MBOAT fold. The MBOAT fold in DGAT1 forms a hollow chamber in the membrane that encloses highly conserved catalytic residues. The chamber has separate entrances for each of the two substrates, fatty acyl-CoA and diacylglycerol. DGAT1 can exist as either a homodimer or a homotetramer and the two forms have similar enzymatic activity. The N terminus of DGAT1 interacts with the neighbouring protomer and these interactions are required for enzymatic activity.

Structure and mechanism of human diacylglycerol O-acyltransferase 1.,Wang L, Qian H, Nian Y, Han Y, Ren Z, Zhang H, Hu L, Prasad BVV, Laganowsky A, Yan N, Zhou M Nature. 2020 May;581(7808):329-332. doi: 10.1038/s41586-020-2280-2. Epub 2020 May, 13. PMID:32433610<ref>PMID:32433610</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6vp0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Han, Y]]
[[Category: Hu, L]]
[[Category: Nian, Y]]
[[Category: Prasad, B V.V]]
[[Category: Qian, H]]
[[Category: Ren, Z]]
[[Category: Wang, L]]
[[Category: Yan, N]]
[[Category: Zhang, H]]
[[Category: Zhou, M]]
[[Category: Diacylglycerol acyltransferase 1]]
[[Category: Er]]
[[Category: Mboat]]
[[Category: Membrane protein]]
[[Category: Oleoyl-coa]]