6vum

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:39, 6 March 2024) (edit) (undo)
 
Line 3: Line 3:
<StructureSection load='6vum' size='340' side='right'caption='[[6vum]], [[Resolution|resolution]] 3.67&Aring;' scene=''>
<StructureSection load='6vum' size='340' side='right'caption='[[6vum]], [[Resolution|resolution]] 3.67&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[6vum]] is a 4 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=6VUM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VUM FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[6vum]] is a 4 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=6VUM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VUM 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=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=ROV:nevanimibe'>ROV</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.67&#8491;</td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SOAT1, ACACT, ACACT1, ACAT, ACAT1, SOAT, STAT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=ROV:nevanimibe'>ROV</scene></td></tr>
-
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Sterol_O-acyltransferase Sterol O-acyltransferase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=6vum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vum OCA], [https://pdbe.org/6vum PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vum RCSB], [https://www.ebi.ac.uk/pdbsum/6vum PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vum 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=6vum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vum OCA], [https://pdbe.org/6vum PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vum RCSB], [https://www.ebi.ac.uk/pdbsum/6vum PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vum ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
-
[[https://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.
+
[https://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 ==
+
-
Cholesterol is an essential component of mammalian cell membranes, constituting up to 50% of plasma membrane lipids. By contrast, it accounts for only 5% of lipids in the endoplasmic reticulum (ER)(1). The ER enzyme sterol O-acyltransferase 1 (also named acyl-coenzyme A:cholesterol acyltransferase, ACAT1) transfers a long-chain fatty acid to cholesterol to form cholesteryl esters that coalesce into cytosolic lipid droplets. Under conditions of cholesterol overload, ACAT1 maintains the low cholesterol concentration of the ER and thereby has an essential role in cholesterol homeostasis(2,3). ACAT1 has also been implicated in Alzheimer's disease(4), atherosclerosis(5) and cancers(6). Here we report a cryo-electron microscopy structure of human ACAT1 in complex with nevanimibe(7), an inhibitor that is in clinical trials for the treatment of congenital adrenal hyperplasia. The ACAT1 holoenzyme is a tetramer that consists of two homodimers. Each monomer contains nine transmembrane helices (TMs), six of which (TM4-TM9) form a cavity that accommodates nevanimibe and an endogenous acyl-coenzyme A. This cavity also contains a histidine that has previously been identified as essential for catalytic activity(8). Our structural data and biochemical analyses provide a physical model to explain the process of cholesterol esterification, as well as details of the interaction between nevanimibe and ACAT1, which may help to accelerate the development of ACAT1 inhibitors to treat related diseases.
+
-
 
+
-
Structure of nevanimibe-bound tetrameric human ACAT1.,Long T, Sun Y, Hassan A, Qi X, Li X Nature. 2020 May;581(7808):339-343. doi: 10.1038/s41586-020-2295-8. Epub 2020 May, 13. PMID:32433613<ref>PMID:32433613</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 6vum" style="background-color:#fffaf0;"></div>
+
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Human]]
+
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Sterol O-acyltransferase]]
+
[[Category: Li X]]
-
[[Category: Li, X]]
+
[[Category: Long T]]
-
[[Category: Long, T]]
+
-
[[Category: Acyltransferase]]
+
-
[[Category: Cholesterol]]
+
-
[[Category: Cholesteryl ester]]
+
-
[[Category: Mboat]]
+
-
[[Category: Membrane protein]]
+

Current revision

Structure of nevanimibe-bound human tetrameric ACAT1

PDB ID 6vum

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6vum"
Personal tools