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6vz1

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Revision as of 15:26, 8 June 2021

Cryo-EM structure of human diacylglycerol O-acyltransferase 1 complexed with acyl-CoA substrate

Structural highlights

6vz1 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	DGAT1, AGRP1, DGAT (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[DGAT1_HUMAN] Congenital chronic diarrhea with protein-losing enteropathy. The disease is caused by mutations affecting the gene represented in this entry.

Function

[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.^[1] ^[2]

Publication Abstract from PubMed

Triacylglycerols store metabolic energy in organisms and have industrial uses as foods and fuels. Excessive accumulation of triacylglycerols in humans causes obesity and is associated with metabolic diseases(1). Triacylglycerol synthesis is catalysed by acyl-CoA diacylglycerol acyltransferase (DGAT) enzymes(2-4), the structures and catalytic mechanisms of which remain unknown. Here we determined the structure of dimeric human DGAT1, a member of the membrane-bound O-acyltransferase (MBOAT) family, by cryo-electron microscopy at approximately 3.0 A resolution. DGAT1 forms a homodimer through N-terminal segments and a hydrophobic interface, with putative active sites within the membrane region. A structure obtained with oleoyl-CoA substrate resolved at approximately 3.2 A shows that the CoA moiety binds DGAT1 on the cytosolic side and the acyl group lies deep within a hydrophobic channel, positioning the acyl-CoA thioester bond near an invariant catalytic histidine residue. The reaction centre is located inside a large cavity, which opens laterally to the membrane bilayer, providing lipid access to the active site. A lipid-like density-possibly representing an acyl-acceptor molecule-is located within the reaction centre, orthogonal to acyl-CoA. Insights provided by the DGAT1 structures, together with mutagenesis and functional studies, provide the basis for a model of the catalysis of triacylglycerol synthesis by DGAT.

Structure and catalytic mechanism of a human triacylglycerol-synthesis enzyme.,Sui X, Wang K, Gluchowski NL, Elliott SD, Liao M, Walther TC, Farese RV Jr Nature. 2020 May;581(7808):323-328. doi: 10.1038/s41586-020-2289-6. Epub 2020 May, 13. PMID:32433611^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Orland MD, Anwar K, Cromley D, Chu CH, Chen L, Billheimer JT, Hussain MM, Cheng D. Acyl coenzyme A dependent retinol esterification by acyl coenzyme A: diacylglycerol acyltransferase 1. Biochim Biophys Acta. 2005 Oct 15;1737(1):76-82. doi:, 10.1016/j.bbalip.2005.09.003. Epub 2005 Sep 20. PMID:16214399 doi:http://dx.doi.org/10.1016/j.bbalip.2005.09.003
↑ Oelkers P, Behari A, Cromley D, Billheimer JT, Sturley SL. Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes. J Biol Chem. 1998 Oct 9;273(41):26765-71. doi: 10.1074/jbc.273.41.26765. PMID:9756920 doi:http://dx.doi.org/10.1074/jbc.273.41.26765
↑ Sui X, Wang K, Gluchowski NL, Elliott SD, Liao M, Walther TC, Farese RV Jr. Structure and catalytic mechanism of a human triacylglycerol-synthesis enzyme. Nature. 2020 May;581(7808):323-328. doi: 10.1038/s41586-020-2289-6. Epub 2020 May, 13. PMID:32433611 doi:http://dx.doi.org/10.1038/s41586-020-2289-6

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6vz1"

@@ Line 3: / Line 3: @@
 <StructureSection load='6vz1' size='340' side='right'caption='[[6vz1]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6vz1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VZ1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VZ1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6vz1]] 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=6VZ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VZ1 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=6OU:[(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl]+(~{Z})-octadec-9-enoate'>6OU</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DGAT1, AGRP1, DGAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://proteopedia.org/fgij/fg.htm?mol=6vz1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vz1 OCA], [http://pdbe.org/6vz1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vz1 RCSB], [http://www.ebi.ac.uk/pdbsum/6vz1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vz1 ProSAT]</span></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=6vz1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vz1 OCA], [https://pdbe.org/6vz1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vz1 RCSB], [https://www.ebi.ac.uk/pdbsum/6vz1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vz1 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://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.
+[[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 ==
-[[http://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>
+[[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 ==

6vz1

From Proteopedia

Revision as of 15:26, 8 June 2021

Cryo-EM structure of human diacylglycerol O-acyltransferase 1 complexed with acyl-CoA substrate

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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