3tvu - Revision history

OCA at 13:41, 14 March 2024

OCA — Thu, 14 Mar 2024 13:41:09 GMT

←Older revision		Revision as of 13:41, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3tvu' size='340' side='right'caption='[[3tvu]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='3tvu' size='340' side='right'caption='[[3tvu]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tvu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Baker's_yeast Baker's yeast~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TVU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tvu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TVU FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=B37:4-({4~~-[~~(2-METHYLQUINOLIN-6-YL)METHYL~~]~~PIPERIDIN-1-YL}CARBONYL)-~~2~~-PHENYLQUINOLINE'>B37</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]] 2.4Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~ACC1, ABP2, FAS3, MTR7, YNR016C, N3175~~ ([~~https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast~~])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B37:4-({4-[(2-METHYLQUINOLIN-6-YL)METHYL]PIPERIDIN-1-YL}CARBONYL)-2-PHENYLQUINOLINE'>B37</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=3tvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvu OCA], [https://pdbe.org/3tvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tvu RCSB], [https://www.ebi.ac.uk/pdbsum/3tvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvu 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=3tvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvu OCA], [https://pdbe.org/3tvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tvu RCSB], [https://www.ebi.ac.uk/pdbsum/3tvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvu ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/ACAC_YEAST ACAC_YEAST]] Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in the synthesis of very-long-chain fatty acid synthesis which is required to maintain a functional nuclear envelope. Required for acylation and vacuolar membrane association of VAC8 which is necessary to maintain a normal morphology of the vacuole.<ref>PMID:6108218</ref> <ref>PMID:6103540</ref> <ref>PMID:8943372</ref> <ref>PMID:10757783</ref> <ref>PMID:12730220</ref>	+	[https://www.uniprot.org/uniprot/ACAC_YEAST ACAC_YEAST] Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in the synthesis of very-long-chain fatty acid synthesis which is required to maintain a functional nuclear envelope. Required for acylation and vacuolar membrane association of VAC8 which is necessary to maintain a normal morphology of the vacuole.<ref>PMID:6108218</ref> <ref>PMID:6103540</ref> <ref>PMID:8943372</ref> <ref>PMID:10757783</ref> <ref>PMID:12730220</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Inhibition of Acetyl-CoA carboxylases (ACCs), a crucial enzyme for fatty acid metabolism, has been shown to promote fatty acid oxidation and reduce body fat in animal models. Therefore, ACCs are attractive targets for structure-based inhibitor design, particularly the carboxyltransferase (CT) domain which is the primary site for inhibitor interaction. We have cloned, expressed and purified the CT domain of human ACC2 using baculovirus mediated insect cell expression system. However, attempts to crystallize the human ACC2 CT domain have not been successful in our hands. Hence, we have been using the available crystal structure of yeast CT domain to design human ACC inhibitors. Unfortunately, as the selectivity of the lead series has increased against the full length human enzyme, the potency against the yeast enzyme has decreased significantly. This loss of potency against the yeast enzyme correlated with a complete lack of binding of the human specific compounds to crystals of the yeast CT domain. Here, we address this problem by converting nine key active site residues of yeast CT domain to the corresponding human residues. The resulting humanized yeast ACC-CT (yCT-H9) protein exhibits biochemical and biophysical properties closer to human CT domain and binding to human specific compounds. We report high resolution crystal structures of yCT-H9 complexed with inhibitors that show a preference for the human CT domain. These structures offer insights which explain the species selectivity of ACC inhibitors and may guide future drug design programs.	+
-		+
-	Structure-guided inhibitor design For human acetyl-coenzyme A charboxylase by interspecies active site conversion.,Rajamohan F, Marr E, Reyes AR, Landro JA, Anderson MD, Corbett JW, Dirico KJ, Harwood JH, Tu M, Vajdos FF J Biol Chem. 2011 Sep 27. PMID:21953464<ref>PMID:21953464</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3tvu" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 26:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Baker's yeast]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Anderson~~, M D~~]]	+	[[Category: Saccharomyces cerevisiae S288C]]
-	[[Category: Corbett~~, J W~~]]	+	[[Category: Anderson MD]]
-	[[Category: Dirico~~, K J~~]]	+	[[Category: Corbett JW]]
-	[[Category: Harwood~~, J H~~]]	+	[[Category: Dirico KJ]]
-	[[Category: Landro~~, J A~~]]	+	[[Category: Harwood JH]]
-	[[Category: Marr, E]]	+	[[Category: Landro JA]]
-	[[Category: Rajamohan, F]]	+	[[Category: Marr E]]
-	[[Category: Reyes, A]]	+	[[Category: Rajamohan F]]
-	[[Category: Tu, M]]	+	[[Category: Reyes A]]
-	[[Category: Vajdos~~, F F]]~~	+	[[Category: Tu M]]
-	~~[[Category: Carboxyltransferase]]~~	+	[[Category: Vajdos FF]]
-	~~[[Category: Ligase~~]]	+

OCA at 05:47, 13 July 2022

OCA — Wed, 13 Jul 2022 05:47:30 GMT

←Older revision		Revision as of 05:47, 13 July 2022
Line 1:		Line 1:

	==Crystal Structure of the humanized carboxyltransferase domain of yeast Acetyl-coA caroxylase in complex with compound 3==		==Crystal Structure of the humanized carboxyltransferase domain of yeast Acetyl-coA caroxylase in complex with compound 3==
-	<StructureSection load='3tvu' size='340' side='right' caption='[[3tvu]], [[Resolution\|resolution]] 2.40Å' scene=''>	+	<StructureSection load='3tvu' size='340' side='right'caption='[[3tvu]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tvu]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3TVU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tvu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TVU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B37:4-({4-[(2-METHYLQUINOLIN-6-YL)METHYL]PIPERIDIN-1-YL}CARBONYL)-2-PHENYLQUINOLINE'>B37</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B37:4-({4-[(2-METHYLQUINOLIN-6-YL)METHYL]PIPERIDIN-1-YL}CARBONYL)-2-PHENYLQUINOLINE'>B37</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACC1, ABP2, FAS3, MTR7, YNR016C, N3175 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACC1, ABP2, FAS3, MTR7, YNR016C, N3175 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=3tvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvu OCA], [~~http~~://pdbe.org/3tvu PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3tvu RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3tvu PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvu 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=3tvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvu OCA], [https://pdbe.org/3tvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tvu RCSB], [https://www.ebi.ac.uk/pdbsum/3tvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvu ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/ACAC_YEAST ACAC_YEAST]] Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in the synthesis of very-long-chain fatty acid synthesis which is required to maintain a functional nuclear envelope. Required for acylation and vacuolar membrane association of VAC8 which is necessary to maintain a normal morphology of the vacuole.<ref>PMID:6108218</ref> <ref>PMID:6103540</ref> <ref>PMID:8943372</ref> <ref>PMID:10757783</ref> <ref>PMID:12730220</ref>	+	[[https://www.uniprot.org/uniprot/ACAC_YEAST ACAC_YEAST]] Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in the synthesis of very-long-chain fatty acid synthesis which is required to maintain a functional nuclear envelope. Required for acylation and vacuolar membrane association of VAC8 which is necessary to maintain a normal morphology of the vacuole.<ref>PMID:6108218</ref> <ref>PMID:6103540</ref> <ref>PMID:8943372</ref> <ref>PMID:10757783</ref> <ref>PMID:12730220</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 3tvu" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3tvu" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Acetyl-CoA carboxylase 3D structures\|Acetyl-CoA carboxylase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Baker's yeast]]		[[Category: Baker's yeast]]
		+	[[Category: Large Structures]]
	[[Category: Anderson, M D]]		[[Category: Anderson, M D]]
	[[Category: Corbett, J W]]		[[Category: Corbett, J W]]

OCA at 19:39, 24 January 2018

OCA — Wed, 24 Jan 2018 19:39:23 GMT

←Older revision		Revision as of 19:39, 24 January 2018
Line 1:		Line 1:
		+
	==Crystal Structure of the humanized carboxyltransferase domain of yeast Acetyl-coA caroxylase in complex with compound 3==		==Crystal Structure of the humanized carboxyltransferase domain of yeast Acetyl-coA caroxylase in complex with compound 3==
	<StructureSection load='3tvu' size='340' side='right' caption='[[3tvu]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='3tvu' size='340' side='right' caption='[[3tvu]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tvu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TVU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tvu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TVU FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B37:4-({4-[(2-METHYLQUINOLIN-6-YL)METHYL]PIPERIDIN-1-YL}CARBONYL)-2-PHENYLQUINOLINE'>B37</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B37:4-({4-[(2-METHYLQUINOLIN-6-YL)METHYL]PIPERIDIN-1-YL}CARBONYL)-2-PHENYLQUINOLINE'>B37</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACC1, ABP2, FAS3, MTR7, YNR016C, N3175 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 ~~Saccharomyces cerevisiae S288c~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACC1, ABP2, FAS3, MTR7, YNR016C, N3175 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=3tvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tvu RCSB], [http://www.ebi.ac.uk/pdbsum/3tvu 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=3tvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvu OCA], [http://pdbe.org/3tvu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tvu RCSB], [http://www.ebi.ac.uk/pdbsum/3tvu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvu 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 3tvu" style="background-color:#fffaf0;"></div>
-	==~~See Also==~~	+
-	*[[Acetyl-CoA carboxylase\|Acetyl-~~CoA carboxylase]]~~	+
-	*[[Biotin carboxylase\|Biotin carboxylase]]	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Saccharomyces cerevisiae s288c~~]]	+	[[Category: Baker's yeast]]
	[[Category: Anderson, M D]]		[[Category: Anderson, M D]]
	[[Category: Corbett, J W]]		[[Category: Corbett, J W]]

OCA at 16:21, 25 December 2014

OCA — Thu, 25 Dec 2014 16:21:33 GMT

←Older revision		Revision as of 16:21, 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=3tvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tvu RCSB], [http://www.ebi.ac.uk/pdbsum/3tvu 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=3tvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tvu RCSB], [http://www.ebi.ac.uk/pdbsum/3tvu PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ACAC_YEAST ACAC_YEAST]] Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in the synthesis of very-long-chain fatty acid synthesis which is required to maintain a functional nuclear envelope. Required for acylation and vacuolar membrane association of VAC8 which is necessary to maintain a normal morphology of the vacuole.<ref>PMID:6108218</ref> <ref>PMID:6103540</ref> <ref>PMID:8943372</ref> <ref>PMID:10757783</ref> <ref>PMID:12730220</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 15:39, 9 December 2014

OCA — Tue, 09 Dec 2014 15:39:52 GMT

←Older revision		Revision as of 15:39, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3tvu.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal Structure of the humanized carboxyltransferase domain of yeast Acetyl-coA caroxylase in complex with compound 3==
		+	<StructureSection load='3tvu' size='340' side='right' caption='[[3tvu]], [[Resolution\|resolution]] 2.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3tvu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TVU FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B37:4-({4-[(2-METHYLQUINOLIN-6-YL)METHYL]PIPERIDIN-1-YL}CARBONYL)-2-PHENYLQUINOLINE'>B37</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACC1, ABP2, FAS3, MTR7, YNR016C, N3175 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Saccharomyces cerevisiae S288c])</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=3tvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tvu RCSB], [http://www.ebi.ac.uk/pdbsum/3tvu PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibition of Acetyl-CoA carboxylases (ACCs), a crucial enzyme for fatty acid metabolism, has been shown to promote fatty acid oxidation and reduce body fat in animal models. Therefore, ACCs are attractive targets for structure-based inhibitor design, particularly the carboxyltransferase (CT) domain which is the primary site for inhibitor interaction. We have cloned, expressed and purified the CT domain of human ACC2 using baculovirus mediated insect cell expression system. However, attempts to crystallize the human ACC2 CT domain have not been successful in our hands. Hence, we have been using the available crystal structure of yeast CT domain to design human ACC inhibitors. Unfortunately, as the selectivity of the lead series has increased against the full length human enzyme, the potency against the yeast enzyme has decreased significantly. This loss of potency against the yeast enzyme correlated with a complete lack of binding of the human specific compounds to crystals of the yeast CT domain. Here, we address this problem by converting nine key active site residues of yeast CT domain to the corresponding human residues. The resulting humanized yeast ACC-CT (yCT-H9) protein exhibits biochemical and biophysical properties closer to human CT domain and binding to human specific compounds. We report high resolution crystal structures of yCT-H9 complexed with inhibitors that show a preference for the human CT domain. These structures offer insights which explain the species selectivity of ACC inhibitors and may guide future drug design programs.

-	~~{{STRUCTURE_3tvu\| PDB=3tvu \| SCENE= }}~~	+	Structure-guided inhibitor design For human acetyl-coenzyme A charboxylase by interspecies active site conversion.,Rajamohan F, Marr E, Reyes AR, Landro JA, Anderson MD, Corbett JW, Dirico KJ, Harwood JH, Tu M, Vajdos FF J Biol Chem. 2011 Sep 27. PMID:21953464<ref>PMID:21953464</ref>

-	~~===Crystal Structure~~ of the ~~humanized carboxyltransferase domain of yeast Acetyl-coA caroxylase in complex with compound 3===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_21953464}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3tvu]] is a 3 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA].~~	+

	==See Also==		==See Also==
	*[[Acetyl-CoA carboxylase\|Acetyl-CoA carboxylase]]		*[[Acetyl-CoA carboxylase\|Acetyl-CoA carboxylase]]
	*[[Biotin carboxylase\|Biotin carboxylase]]		*[[Biotin carboxylase\|Biotin carboxylase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:021953464<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Saccharomyces cerevisiae s288c]]		[[Category: Saccharomyces cerevisiae s288c]]
	[[Category: Anderson, M D]]		[[Category: Anderson, M D]]
-	[[Category: Corbett, J W.]]	+	[[Category: Corbett, J W]]
-	[[Category: Dirico, K J.]]	+	[[Category: Dirico, K J]]
-	[[Category: Harwood, J H.]]	+	[[Category: Harwood, J H]]
-	[[Category: Landro, J A.]]	+	[[Category: Landro, J A]]
-	[[Category: Marr, E.]]	+	[[Category: Marr, E]]
-	[[Category: Rajamohan, F.]]	+	[[Category: Rajamohan, F]]
-	[[Category: Reyes, A.]]	+	[[Category: Reyes, A]]
-	[[Category: Tu, M.]]	+	[[Category: Tu, M]]
-	[[Category: Vajdos, F F.]]	+	[[Category: Vajdos, F F]]
	[[Category: Carboxyltransferase]]		[[Category: Carboxyltransferase]]
	[[Category: Ligase]]		[[Category: Ligase]]

OCA at 18:50, 20 October 2012

OCA — Sat, 20 Oct 2012 18:50:41 GMT

←Older revision		Revision as of 18:50, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3tvu]] is a 3 chain structure ~~of [[Acetyl-CoA carboxylase]] and [[Biotin carboxylase]]~~ with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA].	+	[[3tvu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA].

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

OCA at 05:25, 27 July 2012

OCA — Fri, 27 Jul 2012 05:25:23 GMT

←Older revision		Revision as of 05:25, 27 July 2012
Line 1:		Line 1:
	[[Image:3tvu.png\|left\|200px]]		[[Image:3tvu.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3tvu", 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_3tvu\| PDB=3tvu \| SCENE= }}		{{STRUCTURE_3tvu\| PDB=3tvu \| SCENE= }}

	===Crystal Structure of the humanized carboxyltransferase domain of yeast Acetyl-coA caroxylase in complex with compound 3===		===Crystal Structure of the humanized carboxyltransferase domain of yeast Acetyl-coA caroxylase in complex with compound 3===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21953464}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21953464 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_21953464}}		{{ABSTRACT_PUBMED_21953464}}

	==About this Structure==		==About this Structure==
-	[[3tvu]] is a 3 chain structure of [[Biotin carboxylase]] with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA].	+	[[3tvu]] is a 3 chain structure of [[Acetyl-CoA carboxylase]] and [[Biotin carboxylase]] with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA].

	==See Also==		==See Also==
-	*[[Biotin carboxylase]]	+	*[[Acetyl-CoA carboxylase\|Acetyl-CoA carboxylase]]
		+	*[[Biotin carboxylase\|Biotin carboxylase]]

	==Reference==		==Reference==

OCA at 10:45, 14 December 2011

OCA — Wed, 14 Dec 2011 10:45:12 GMT

←Older revision		Revision as of 10:45, 14 December 2011
Line 19:		Line 19:

	==About this Structure==		==About this Structure==
-	[[3tvu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA].	+	[[3tvu]] is a 3 chain structure of [[Biotin carboxylase]] with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA].
		+
		+	==See Also==
		+	*[[Biotin carboxylase]]

	==Reference==		==Reference==

OCA at 10:24, 30 October 2011

OCA — Sun, 30 Oct 2011 10:24:53 GMT

←Older revision		Revision as of 10:24, 30 October 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3tvu.png\|left\|200px]]

-	The ~~entry 3tvu~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3tvu", 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_3tvu\| PDB=3tvu \| SCENE= }}

-	~~Authors: Rajamohan, F., Marr, E., Reyes, A., Landro, J.A., Anderson, M.D, Corbett, J.W., Dirico, K.J., Harwood, J.H., Tu. M., Vajdos, F.F.~~	+	===Crystal Structure of the humanized carboxyltransferase domain of yeast Acetyl-coA caroxylase in complex with compound 3===

-	~~Description~~: ~~Crystal Structure of~~ the ~~humanized carboxyltransferase domain of yeast Acetyl~~-~~coA caroxylase in complex with compound~~ 3	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21953464}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21953464 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21953464}}
		+
		+	==About this Structure==
		+	[[3tvu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVU OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021953464</ref><references group="xtra"/>
		+	[[Category: Saccharomyces cerevisiae s288c]]
		+	[[Category: Anderson, M D]]
		+	[[Category: Corbett, J W.]]
		+	[[Category: Dirico, K J.]]
		+	[[Category: Harwood, J H.]]
		+	[[Category: Landro, J A.]]
		+	[[Category: Marr, E.]]
		+	[[Category: Rajamohan, F.]]
		+	[[Category: Reyes, A.]]
		+	[[Category: Tu, M.]]
		+	[[Category: Vajdos, F F.]]
		+	[[Category: Carboxyltransferase]]
		+	[[Category: Ligase]]

OCA at 06:11, 5 October 2011

OCA — Wed, 05 Oct 2011 06:11:48 GMT

←Older revision		Revision as of 06:11, 5 October 2011
Line 3:		Line 3:
	The entry 3tvu is ON HOLD		The entry 3tvu is ON HOLD

-	Authors: Rajamohan, F., Marr, E., Reyes, A., Landro, J. A., Anderson, M. D, Corbett, J. W., Dirico, K. J., Harwood, J. H., Tu. M., Vajdos, F. F.	+	Authors: Rajamohan, F., Marr, E., Reyes, A., Landro, J.A., Anderson, M.D, Corbett, J.W., Dirico, K.J., Harwood, J.H., Tu. M., Vajdos, F.F.

	Description: Crystal Structure of the humanized carboxyltransferase domain of yeast Acetyl-coA caroxylase in complex with compound 3		Description: Crystal Structure of the humanized carboxyltransferase domain of yeast Acetyl-coA caroxylase in complex with compound 3