3tjm - Revision history

OCA at 13:31, 14 March 2024

OCA — Thu, 14 Mar 2024 13:31:04 GMT

←Older revision		Revision as of 13:31, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3tjm' size='340' side='right'caption='[[3tjm]], [[Resolution\|resolution]] 1.48Å' scene=''>		<StructureSection load='3tjm' size='340' side='right'caption='[[3tjm]], [[Resolution\|resolution]] 1.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tjm]] is a 1 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=3TJM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TJM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tjm]] 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=3TJM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TJM FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=7FA:METHYL+(R)~~-~~(6Z~~,~~9Z,12Z)-OCTADECA-6,9,12-TRIEN-~~1~~-YLPHOSPHONOFLUORIDATE'>7FA</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.48Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~FAS, FASN ([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=7FA:METHYL+(R)-(6Z,9Z,12Z)-OCTADECA-6,9,12-TRIEN-1-YLPHOSPHONOFLUORIDATE'>7FA</scene></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=3tjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjm OCA], [https://pdbe.org/3tjm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tjm RCSB], [https://www.ebi.ac.uk/pdbsum/3tjm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tjm 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=3tjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjm OCA], [https://pdbe.org/3tjm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tjm RCSB], [https://www.ebi.ac.uk/pdbsum/3tjm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tjm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/FAS_HUMAN FAS_HUMAN]] Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein.	+	[https://www.uniprot.org/uniprot/FAS_HUMAN FAS_HUMAN] Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Human fatty acid synthase (hFAS) is a homodimeric multidomain enzyme that catalyzes a series of reactions leading to the de novo biosynthesis of long-chain fatty acids, mainly palmitate. The carboxy-terminal thioesterase (TE) domain determines the length of the fatty acyl chain and its ultimate release by hydrolysis. Because of the upregulation of hFAS in a variety of cancers, it is a target for antiproliferative agent development. Dietary long-chain polyunsaturated fatty acids (PUFAs) have been known to confer beneficial effects on many diseases and health conditions, including cancers, inflammations, diabetes, and heart diseases, but the precise molecular mechanisms involved have not been elucidated. We report the crystal structure of the hFAS TE domain covalently modified and inactivated by methyl gamma-linolenylfluorophosphonate. Whereas the structure confirmed the phosphorylation by the phosphonate head group of the active site serine, it also unexpectedly revealed the binding of the 18-carbon polyunsaturated gamma-linolenyl tail in a long groove-tunnel site, which itself is formed mainly by the emergence of an alpha helix (the "helix flap"). We then found inhibition of the TE domain activity by the PUFA dihomo-gamma-linolenic acid; gamma- and alpha-linolenic acids, two popular dietary PUFAs, were less effective. Dihomo-gamma-linolenic acid also inhibited fatty acid biosynthesis in 3T3-L1 preadipocytes and selective human breast cancer cell lines, including SKBR3 and MDAMB231. In addition to revealing a novel mechanism for the molecular recognition of a polyunsaturated fatty acyl chain, our results offer a new framework for developing potent FAS inhibitors as therapeutics against cancers and other diseases.	+
-		+
-	Crystal structure of FAS thioesterase domain with polyunsaturated fatty acyl adduct and inhibition by dihomo-{gamma}-linolenic acid.,Zhang W, Chakravarty B, Zheng F, Gu Z, Wu H, Mao J, Wakil SJ, Quiocho FA Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15757-62. Epub 2011 Sep 9. PMID:21908709<ref>PMID:21908709</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3tjm" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
	*[[Fatty acid synthase\|Fatty acid synthase]]		*[[Fatty acid synthase\|Fatty acid synthase]]
	*[[Fatty acid synthase 3D structures\|Fatty acid synthase 3D structures]]		*[[Fatty acid synthase 3D structures\|Fatty acid synthase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Florante~~, A Q~~]]	+	[[Category: Florante AQ]]
-	[[Category: Zhang, W]]	+	[[Category: Zhang W]]
-	[[Category: Zheng, F]]	+	[[Category: Zheng F]]
-	~~[[Category: Fatty acid synthesis]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Thioesterase domain~~]]	+

OCA at 17:01, 6 July 2022

OCA — Wed, 06 Jul 2022 17:01:01 GMT

←Older revision		Revision as of 17:01, 6 July 2022
Line 3:		Line 3:
	<StructureSection load='3tjm' size='340' side='right'caption='[[3tjm]], [[Resolution\|resolution]] 1.48Å' scene=''>		<StructureSection load='3tjm' size='340' side='right'caption='[[3tjm]], [[Resolution\|resolution]] 1.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tjm]] is a 1 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=3TJM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3TJM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tjm]] is a 1 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=3TJM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TJM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7FA:METHYL+(R)-(6Z,9Z,12Z)-OCTADECA-6,9,12-TRIEN-1-YLPHOSPHONOFLUORIDATE'>7FA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7FA:METHYL+(R)-(6Z,9Z,12Z)-OCTADECA-6,9,12-TRIEN-1-YLPHOSPHONOFLUORIDATE'>7FA</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FAS, FASN ([~~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">FAS, FASN ([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~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3tjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjm OCA], [~~http~~://pdbe.org/3tjm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3tjm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3tjm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3tjm 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=3tjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjm OCA], [https://pdbe.org/3tjm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tjm RCSB], [https://www.ebi.ac.uk/pdbsum/3tjm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tjm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/FAS_HUMAN FAS_HUMAN]] Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein.	+	[[https://www.uniprot.org/uniprot/FAS_HUMAN FAS_HUMAN]] Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 11:41, 17 July 2019

OCA — Wed, 17 Jul 2019 11:41:00 GMT

←Older revision		Revision as of 11:41, 17 July 2019
Line 1:		Line 1:

	==Crystal Structure of the Human Fatty Acid Synthase Thioesterase Domain with an Activate Site-Specific Polyunsaturated Fatty Acyl Adduct==		==Crystal Structure of the Human Fatty Acid Synthase Thioesterase Domain with an Activate Site-Specific Polyunsaturated Fatty Acyl Adduct==
-	<StructureSection load='3tjm' size='340' side='right' caption='[[3tjm]], [[Resolution\|resolution]] 1.48Å' scene=''>	+	<StructureSection load='3tjm' size='340' side='right'caption='[[3tjm]], [[Resolution\|resolution]] 1.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3tjm]] is a 1 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=3TJM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJM FirstGlance]. <br>		<table><tr><td colspan='2'>[[3tjm]] is a 1 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=3TJM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJM FirstGlance]. <br>
Line 22:		Line 22:
	==See Also==		==See Also==
	*[[Fatty acid synthase\|Fatty acid synthase]]		*[[Fatty acid synthase\|Fatty acid synthase]]
		+	*[[Fatty acid synthase 3D structures\|Fatty acid synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Florante, A Q]]		[[Category: Florante, A Q]]
	[[Category: Zhang, W]]		[[Category: Zhang, W]]

OCA at 02:24, 5 August 2016

OCA — Fri, 05 Aug 2016 02:24:58 GMT

←Older revision		Revision as of 02:24, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of the Human Fatty Acid Synthase Thioesterase Domain with an Activate Site-Specific Polyunsaturated Fatty Acyl Adduct==		==Crystal Structure of the Human Fatty Acid Synthase Thioesterase Domain with an Activate Site-Specific Polyunsaturated Fatty Acyl Adduct==
	<StructureSection load='3tjm' size='340' side='right' caption='[[3tjm]], [[Resolution\|resolution]] 1.48Å' scene=''>		<StructureSection load='3tjm' size='340' side='right' caption='[[3tjm]], [[Resolution\|resolution]] 1.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tjm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tjm]] is a 1 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=3TJM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7FA:METHYL+(S)-(6Z,9Z)-OCTADECA-6,9,12-TRIEN-1-YLPHOSPHONOFLUORIDATE'>7FA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7FA:METHYL+(R)-(6Z,9Z,12Z)-OCTADECA-6,9,12-TRIEN-1-YLPHOSPHONOFLUORIDATE'>7FA</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FAS, FASN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FAS, FASN ([http://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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tjm RCSB], [http://www.ebi.ac.uk/pdbsum/3tjm PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjm OCA], [http://pdbe.org/3tjm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tjm RCSB], [http://www.ebi.ac.uk/pdbsum/3tjm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tjm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3tjm" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 24:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Florante, A Q]]		[[Category: Florante, A Q]]
	[[Category: Zhang, W]]		[[Category: Zhang, W]]

OCA at 15:05, 25 December 2014

OCA — Thu, 25 Dec 2014 15:05:27 GMT

←Older revision		Revision as of 15:05, 25 December 2014
Line 7:		Line 7:
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tjm RCSB], [http://www.ebi.ac.uk/pdbsum/3tjm PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tjm RCSB], [http://www.ebi.ac.uk/pdbsum/3tjm PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FAS_HUMAN FAS_HUMAN]] Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 17:49, 9 December 2014

OCA — Tue, 09 Dec 2014 17:49:12 GMT

←Older revision		Revision as of 17:49, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3tjm.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal Structure of the Human Fatty Acid Synthase Thioesterase Domain with an Activate Site-Specific Polyunsaturated Fatty Acyl Adduct==
		+	<StructureSection load='3tjm' size='340' side='right' caption='[[3tjm]], [[Resolution\|resolution]] 1.48Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3tjm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJM FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7FA:METHYL+(S)-(6Z,9Z)-OCTADECA-6,9,12-TRIEN-1-YLPHOSPHONOFLUORIDATE'>7FA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FAS, FASN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tjm RCSB], [http://www.ebi.ac.uk/pdbsum/3tjm PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human fatty acid synthase (hFAS) is a homodimeric multidomain enzyme that catalyzes a series of reactions leading to the de novo biosynthesis of long-chain fatty acids, mainly palmitate. The carboxy-terminal thioesterase (TE) domain determines the length of the fatty acyl chain and its ultimate release by hydrolysis. Because of the upregulation of hFAS in a variety of cancers, it is a target for antiproliferative agent development. Dietary long-chain polyunsaturated fatty acids (PUFAs) have been known to confer beneficial effects on many diseases and health conditions, including cancers, inflammations, diabetes, and heart diseases, but the precise molecular mechanisms involved have not been elucidated. We report the crystal structure of the hFAS TE domain covalently modified and inactivated by methyl gamma-linolenylfluorophosphonate. Whereas the structure confirmed the phosphorylation by the phosphonate head group of the active site serine, it also unexpectedly revealed the binding of the 18-carbon polyunsaturated gamma-linolenyl tail in a long groove-tunnel site, which itself is formed mainly by the emergence of an alpha helix (the "helix flap"). We then found inhibition of the TE domain activity by the PUFA dihomo-gamma-linolenic acid; gamma- and alpha-linolenic acids, two popular dietary PUFAs, were less effective. Dihomo-gamma-linolenic acid also inhibited fatty acid biosynthesis in 3T3-L1 preadipocytes and selective human breast cancer cell lines, including SKBR3 and MDAMB231. In addition to revealing a novel mechanism for the molecular recognition of a polyunsaturated fatty acyl chain, our results offer a new framework for developing potent FAS inhibitors as therapeutics against cancers and other diseases.

-	{~~{STRUCTURE_3tjm\| PDB=3tjm \| SCENE= }~~}	+	Crystal structure of FAS thioesterase domain with polyunsaturated fatty acyl adduct and inhibition by dihomo-{gamma}-linolenic acid.,Zhang W, Chakravarty B, Zheng F, Gu Z, Wu H, Mao J, Wakil SJ, Quiocho FA Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15757-62. Epub 2011 Sep 9. PMID:21908709<ref>PMID:21908709</ref>

-	~~===Crystal Structure~~ of the ~~Human Fatty Acid Synthase Thioesterase Domain with an Activate Site-Specific Polyunsaturated Fatty Acyl Adduct===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_21908709}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3tjm]] is a 1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3TJM OCA].~~	+

	==See Also==		==See Also==
	*[[Fatty acid synthase\|Fatty acid synthase]]		*[[Fatty acid synthase\|Fatty acid synthase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:021908709<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Florante, A Q.]]	+	[[Category: Florante, A Q]]
-	[[Category: Zhang, W.]]	+	[[Category: Zhang, W]]
-	[[Category: Zheng, F.]]	+	[[Category: Zheng, F]]
	[[Category: Fatty acid synthesis]]		[[Category: Fatty acid synthesis]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Thioesterase domain]]		[[Category: Thioesterase domain]]

OCA at 18:07, 20 October 2012

OCA — Sat, 20 Oct 2012 18:07:38 GMT

←Older revision		Revision as of 18:07, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3tjm]] is a 1 chain structure ~~of [[Fatty acid synthase]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJM OCA].	+	[[3tjm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJM OCA].

	==See Also==		==See Also==

OCA at 03:06, 27 July 2012

OCA — Fri, 27 Jul 2012 03:06:08 GMT

←Older revision		Revision as of 03:06, 27 July 2012
Line 1:		Line 1:
	[[Image:3tjm.png\|left\|200px]]		[[Image:3tjm.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3tjm", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3tjm\| PDB=3tjm \| SCENE= }}		{{STRUCTURE_3tjm\| PDB=3tjm \| SCENE= }}

	===Crystal Structure of the Human Fatty Acid Synthase Thioesterase Domain with an Activate Site-Specific Polyunsaturated Fatty Acyl Adduct===		===Crystal Structure of the Human Fatty Acid Synthase Thioesterase Domain with an Activate Site-Specific Polyunsaturated Fatty Acyl Adduct===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21908709}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21908709 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_21908709}}		{{ABSTRACT_PUBMED_21908709}}

	==About this Structure==		==About this Structure==
-	[[3tjm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJM OCA].	+	[[3tjm]] is a 1 chain structure of [[Fatty acid synthase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJM OCA].
		+
		+	==See Also==
		+	*[[Fatty acid synthase\|Fatty acid synthase]]

	==Reference==		==Reference==

OCA at 11:26, 16 November 2011

OCA — Wed, 16 Nov 2011 11:26:24 GMT

←Older revision		Revision as of 11:26, 16 November 2011
Line 1:		Line 1:
-	[[Image:3tjm.~~jpg~~\|left\|200px]]	+	[[Image:3tjm.png\|left\|200px]]

	<!--		<!--

OCA at 05:38, 28 September 2011

OCA — Wed, 28 Sep 2011 05:38:15 GMT

←Older revision		Revision as of 05:38, 28 September 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3tjm.jpg\|left\|200px]]

-	The ~~entry 3tjm~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3tjm", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3tjm\| PDB=3tjm \| SCENE= }}

-	~~Authors: Zhang, W., Zheng, F., Florante, A.Q.~~	+	===Crystal Structure of the Human Fatty Acid Synthase Thioesterase Domain with an Activate Site-Specific Polyunsaturated Fatty Acyl Adduct===

-	~~Description~~: ~~Crystal Structure of~~ the ~~Human Fatty Acid Synthase Thioesterase Domain~~ with ~~an Activate Site~~-~~Specific Polyunsaturated~~ Fatty ~~Acyl Adduct~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21908709}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21908709 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21908709}}
		+
		+	==About this Structure==
		+	[[3tjm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJM OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021908709</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Florante, A Q.]]
		+	[[Category: Zhang, W.]]
		+	[[Category: Zheng, F.]]
		+	[[Category: Fatty acid synthesis]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Thioesterase domain]]