6p2p: Difference between revisions
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==Tetrameric structure of ACAT1== | ==Tetrameric structure of ACAT1== | ||
<StructureSection load='6p2p' size='340' side='right'caption='[[6p2p]]' scene=''> | <StructureSection load='6p2p' size='340' side='right'caption='[[6p2p]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P2P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6P2P FirstGlance]. <br> | <table><tr><td colspan='2'>[[6p2p]] is a 4 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=6P2P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6P2P FirstGlance]. <br> | ||
</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=6p2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p2p OCA], [http://pdbe.org/6p2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p2p RCSB], [http://www.ebi.ac.uk/pdbsum/6p2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p2p ProSAT]</span></td></tr> | </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></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SOAT1, ACACT, ACACT1, ACAT, ACAT1, SOAT, STAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Sterol_O-acyltransferase Sterol O-acyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.26 2.3.1.26] </span></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=6p2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p2p OCA], [http://pdbe.org/6p2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p2p RCSB], [http://www.ebi.ac.uk/pdbsum/6p2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p2p ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/SOAT1_HUMAN SOAT1_HUMAN]] Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition to its acyltransferase activity, it may act as a ligase. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
As members of the membrane-bound O-acyltransferase (MBOAT) enzyme family, acyl-coenzyme A:cholesterol acyltransferases (ACATs) catalyse the transfer of an acyl group from acyl-coenzyme A to cholesterol to generate cholesteryl ester, the primary form in which cholesterol is stored in cells and transported in plasma(1). ACATs have gained attention as potential drug targets for the treatment of diseases such as atherosclerosis, Alzheimer's disease and cancer(2-7). Here we present the cryo-electron microscopy structure of human ACAT1 as a dimer of dimers. Each protomer consists of nine transmembrane segments, which enclose a cytosolic tunnel and a transmembrane tunnel that converge at the predicted catalytic site. Evidence from structure-guided mutational analyses suggests that acyl-coenzyme A enters the active site through the cytosolic tunnel, whereas cholesterol may enter from the side through the transmembrane tunnel. This structural and biochemical characterization helps to rationalize the preference of ACAT1 for unsaturated acyl chains, and provides insight into the catalytic mechanism of enzymes within the MBOAT family(8). | |||
Structural basis for catalysis and substrate specificity of human ACAT1.,Qian H, Zhao X, Yan R, Yao X, Gao S, Sun X, Du X, Yang H, Wong CCL, Yan N Nature. 2020 May;581(7808):333-338. doi: 10.1038/s41586-020-2290-0. Epub 2020 May, 13. PMID:32433614<ref>PMID:32433614</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6p2p" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Qian | [[Category: Sterol O-acyltransferase]] | ||
[[Category: Yan N]] | [[Category: Qian, H W]] | ||
[[Category: Yan, N]] | |||
[[Category: Mboat]] | |||
[[Category: Transferase]] | |||
Revision as of 09:35, 3 June 2020
Tetrameric structure of ACAT1Tetrameric structure of ACAT1
Structural highlights
Function[SOAT1_HUMAN] Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition to its acyltransferase activity, it may act as a ligase. Publication Abstract from PubMedAs members of the membrane-bound O-acyltransferase (MBOAT) enzyme family, acyl-coenzyme A:cholesterol acyltransferases (ACATs) catalyse the transfer of an acyl group from acyl-coenzyme A to cholesterol to generate cholesteryl ester, the primary form in which cholesterol is stored in cells and transported in plasma(1). ACATs have gained attention as potential drug targets for the treatment of diseases such as atherosclerosis, Alzheimer's disease and cancer(2-7). Here we present the cryo-electron microscopy structure of human ACAT1 as a dimer of dimers. Each protomer consists of nine transmembrane segments, which enclose a cytosolic tunnel and a transmembrane tunnel that converge at the predicted catalytic site. Evidence from structure-guided mutational analyses suggests that acyl-coenzyme A enters the active site through the cytosolic tunnel, whereas cholesterol may enter from the side through the transmembrane tunnel. This structural and biochemical characterization helps to rationalize the preference of ACAT1 for unsaturated acyl chains, and provides insight into the catalytic mechanism of enzymes within the MBOAT family(8). Structural basis for catalysis and substrate specificity of human ACAT1.,Qian H, Zhao X, Yan R, Yao X, Gao S, Sun X, Du X, Yang H, Wong CCL, Yan N Nature. 2020 May;581(7808):333-338. doi: 10.1038/s41586-020-2290-0. Epub 2020 May, 13. PMID:32433614[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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