8erc - Revision history

OCA at 09:03, 4 June 2025

2025-06-04T09:03:00Z

← Older revision		Revision as of 09:03, 4 June 2025
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	[https://www.uniprot.org/uniprot/MBOA7_HUMAN MBOA7_HUMAN] Autosomal recessive non-syndromic intellectual disability. The disease is caused by variants affecting the gene represented in this entry.		[https://www.uniprot.org/uniprot/MBOA7_HUMAN MBOA7_HUMAN] Autosomal recessive non-syndromic intellectual disability. The disease is caused by variants affecting the gene represented in this entry.
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/MBOA7_HUMAN MBOA7_HUMAN] Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA to a lysophosphatidylinositol (1-acylglycerophosphatidylinositol or LPI) leading to the production of a phosphatidylinositol (1,2-diacyl-sn-glycero-3-phosphoinositol or PI) and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle (PubMed:~~18772128~~, PubMed:~~18094042~~). Prefers arachidonoyl-CoA as the acyl donor, thus contributing to the regulation of free levels arachidonic acid in cell (PubMed:~~18772128~~, PubMed:~~18094042~~). In liver, participates in the regulation of triglyceride metabolism through the phosphatidylinositol acyl-chain remodeling regulation (PubMed:32253259).<ref>PMID:18094042</ref> <ref>PMID:18772128</ref> <ref>PMID:32253259</ref>		[https://www.uniprot.org/uniprot/MBOA7_HUMAN MBOA7_HUMAN] Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA to a lysophosphatidylinositol (1-acylglycerophosphatidylinositol or LPI) leading to the production of a phosphatidylinositol (1,2-diacyl-sn-glycero-3-phosphoinositol or PI) and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle (PubMed:18094042, PubMed:18772128). Prefers arachidonoyl-CoA as the acyl donor, thus contributing to the regulation of free levels arachidonic acid in cell (PubMed:18094042, PubMed:18772128). In liver, participates in the regulation of triglyceride metabolism through the phosphatidylinositol acyl-chain remodeling regulation (PubMed:32253259).<ref>PMID:18094042</ref> <ref>PMID:18772128</ref> <ref>PMID:32253259</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Cells remodel glycerophospholipid acyl chains via the Lands cycle to adjust membrane properties. Membrane-bound O-acyltransferase (MBOAT) 7 acylates lyso-phosphatidylinositol (lyso-PI) with arachidonyl-CoA. MBOAT7 mutations cause brain developmental disorders, and reduced expression is linked to fatty liver disease. In contrast, increased MBOAT7 expression is linked to hepatocellular and renal cancers. The mechanistic basis of MBOAT7 catalysis and substrate selectivity are unknown. Here, we report the structure and a model for the catalytic mechanism of human MBOAT7. Arachidonyl-CoA and lyso-PI access the catalytic center through a twisted tunnel from the cytosol and lumenal sides, respectively. N-terminal residues on the ER lumenal side determine phospholipid headgroup selectivity: swapping them between MBOATs 1, 5, and 7 converts enzyme specificity for different lyso-phospholipids. Finally, the MBOAT7 structure and virtual screening enabled identification of small-molecule inhibitors that may serve as lead compounds for pharmacologic development.

	The structure of phosphatidylinositol remodeling MBOAT7 reveals its catalytic mechanism and enables inhibitor identification.,Wang K, Lee CW, Sui X, Kim S, Wang S, Higgs AB, Baublis AJ, Voth GA, Liao M, Walther TC, Farese RV Jr Nat Commun. 2023 Jun 14;14(1):3533. doi: 10.1038/s41467-023-38932-5. PMID:37316513<ref>PMID:37316513</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 8erc" style="background-color:#fffaf0;"></div~~>
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:56, 27 September 2023

2023-09-27T06:56:23Z

← Older revision		Revision as of 06:56, 27 September 2023
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	~~'''Unreleased structure'''~~

	The entry ~~8erc~~ is ~~ON HOLD until Paper Publication~~		==Human Membrane-bound O-acyltransferase 7==
			<StructureSection load='8erc' size='340' side='right'caption='[[8erc]], [[Resolution\|resolution]] 3.70Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[8erc]] is a 1 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=8ERC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ERC FirstGlance]. <br>
			</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.7Å</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=8erc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8erc OCA], [https://pdbe.org/8erc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8erc RCSB], [https://www.ebi.ac.uk/pdbsum/8erc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8erc ProSAT]</span></td></tr>
			</table>
			== Disease ==
			[https://www.uniprot.org/uniprot/MBOA7_HUMAN MBOA7_HUMAN] Autosomal recessive non-syndromic intellectual disability. The disease is caused by variants affecting the gene represented in this entry.
			== Function ==
			[https://www.uniprot.org/uniprot/MBOA7_HUMAN MBOA7_HUMAN] Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA to a lysophosphatidylinositol (1-acylglycerophosphatidylinositol or LPI) leading to the production of a phosphatidylinositol (1,2-diacyl-sn-glycero-3-phosphoinositol or PI) and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle (PubMed:18772128, PubMed:18094042). Prefers arachidonoyl-CoA as the acyl donor, thus contributing to the regulation of free levels arachidonic acid in cell (PubMed:18772128, PubMed:18094042). In liver, participates in the regulation of triglyceride metabolism through the phosphatidylinositol acyl-chain remodeling regulation (PubMed:32253259).<ref>PMID:18094042</ref> <ref>PMID:18772128</ref> <ref>PMID:32253259</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Cells remodel glycerophospholipid acyl chains via the Lands cycle to adjust membrane properties. Membrane-bound O-acyltransferase (MBOAT) 7 acylates lyso-phosphatidylinositol (lyso-PI) with arachidonyl-CoA. MBOAT7 mutations cause brain developmental disorders, and reduced expression is linked to fatty liver disease. In contrast, increased MBOAT7 expression is linked to hepatocellular and renal cancers. The mechanistic basis of MBOAT7 catalysis and substrate selectivity are unknown. Here, we report the structure and a model for the catalytic mechanism of human MBOAT7. Arachidonyl-CoA and lyso-PI access the catalytic center through a twisted tunnel from the cytosol and lumenal sides, respectively. N-terminal residues on the ER lumenal side determine phospholipid headgroup selectivity: swapping them between MBOATs 1, 5, and 7 converts enzyme specificity for different lyso-phospholipids. Finally, the MBOAT7 structure and virtual screening enabled identification of small-molecule inhibitors that may serve as lead compounds for pharmacologic development.

	~~Authors:~~ Wang, K., Liao, M., Farese~~, R~~.V.~~, Walther, T~~.C.		The structure of phosphatidylinositol remodeling MBOAT7 reveals its catalytic mechanism and enables inhibitor identification.,Wang K, Lee CW, Sui X, Kim S, Wang S, Higgs AB, Baublis AJ, Voth GA, Liao M, Walther TC, Farese RV Jr Nat Commun. 2023 Jun 14;14(1):3533. doi: 10.1038/s41467-023-38932-5. PMID:37316513<ref>PMID:37316513</ref>

	~~Description: Human Membrane~~-~~bound O~~-~~acyltransferase 7~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased~~ Structures]]		</div>
	[[Category: Farese~~, R.V~~]]		<div class="pdbe-citations 8erc" style="background-color:#fffaf0;"></div>
	[[Category: Liao, M]]		== References ==
	[[Category: ~~Wang, K~~]]		<references/>
	[[Category: ~~Walther, T.C~~]]		__TOC__
			</StructureSection>
			[[Category: Homo sapiens]]
			[[Category: Large Structures]]
			[[Category: Farese RV]]
			[[Category: Liao M]]
			[[Category: Walther TC]]
			[[Category: Wang K]]

OCA at 04:00, 26 October 2022

2022-10-26T04:00:35Z

← Older revision		Revision as of 04:00, 26 October 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8erc is ON HOLD		The entry 8erc is ON HOLD until Paper Publication

	Authors: Wang, K., Liao, M., Farese, R.V., Walther, T.C.		Authors: Wang, K., Liao, M., Farese, R.V., Walther, T.C.

OCA: Protected "8erc" [edit=sysop:move=sysop]

2022-10-19T17:29:02Z

Protected "8erc" [edit=sysop:move=sysop]

← Older revision	Revision as of 17:29, 19 October 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8erc is ON HOLD Authors: Wang, K., Liao, M., Farese, R.V., Walther, T.C. Description: Human Membrane-bound O-acyltransferase 7 [[Category: Unreleas...

2022-10-19T17:28:58Z

New page: '''Unreleased structure''' The entry 8erc is ON HOLD Authors: Wang, K., Liao, M., Farese, R.V., Walther, T.C. Description: Human Membrane-bound O-acyltransferase 7 [[Category: Unreleas...

New page

'''Unreleased structure'''

The entry 8erc is ON HOLD

Authors: Wang, K., Liao, M., Farese, R.V., Walther, T.C.

Description: Human Membrane-bound O-acyltransferase 7
[[Category: Unreleased Structures]]
[[Category: Farese, R.V]]
[[Category: Liao, M]]
[[Category: Wang, K]]
[[Category: Walther, T.C]]