5duc - Revision history

OCA at 22:00, 28 June 2023

2023-06-28T22:00:15Z

← Older revision		Revision as of 22:00, 28 June 2023
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	<StructureSection load='5duc' size='340' side='right'caption='[[5duc]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='5duc' size='340' side='right'caption='[[5duc]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5duc]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus~~ tuberculosis~~" (zopf 1883) klein 1884~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DUC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5DUC FirstGlance]. <br>		<table><tr><td colspan='2'>[[5duc]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DUC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G51:(5R,7S)-N-(1,3-BENZODIOXOL-5-YLMETHYL)-5-(4-ETHYLPHENYL)-7-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE'>G51</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]] 2.704Å</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">echA6, Rv0905, MTCY31.33 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G51:(5R,7S)-N-(1,3-BENZODIOXOL-5-YLMETHYL)-5-(4-ETHYLPHENYL)-7-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE'>G51</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-CoA_hydratase Enoyl-CoA hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.17 4.2.1.17] </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=5duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5duc OCA], [https://pdbe.org/5duc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5duc RCSB], [https://www.ebi.ac.uk/pdbsum/5duc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5duc ProSAT]</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=5duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5duc OCA], [~~http~~://pdbe.org/5duc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5duc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5duc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5duc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/ECHA6_MYCTU ECHA6_MYCTU]] Could possibly oxidize fatty acids using specific components.		[https://www.uniprot.org/uniprot/ECHA6_MYCTU ECHA6_MYCTU] Could possibly oxidize fatty acids using specific components.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Enoyl-CoA hydratase]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Besra, G S~~]]		[[Category: Mycobacterium tuberculosis]]
	[[Category: ~~Cox, J A.G~~]]		[[Category: Besra GS]]
	[[Category: ~~Futterer, K~~]]		[[Category: Cox JAG]]
	[[Category: ~~Enoyl-coa hydratase-like]]~~		[[Category: Futterer K]]
	~~[[Category: Lipid binding protein]]~~
	~~[[Category: Lyase~~]]

OCA at 08:06, 15 April 2020

2020-04-15T08:06:24Z

← Older revision		Revision as of 08:06, 15 April 2020
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	==Crystal structure of M. tuberculosis EchA6 bound to ligand GSK951A==		==Crystal structure of M. tuberculosis EchA6 bound to ligand GSK951A==
	<StructureSection load='5duc' size='340' side='right' caption='[[5duc]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='5duc' size='340' side='right'caption='[[5duc]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5duc]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DUC OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca.weizmann.ac~~.~~il/oca-docs~~/fgij/fg.htm?mol=5DUC FirstGlance]. <br>		<table><tr><td colspan='2'>[[5duc]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DUC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DUC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G51:(5R,7S)-N-(1,3-BENZODIOXOL-5-YLMETHYL)-5-(4-ETHYLPHENYL)-7-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE'>G51</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G51:(5R,7S)-N-(1,3-BENZODIOXOL-5-YLMETHYL)-5-(4-ETHYLPHENYL)-7-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE'>G51</scene></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">echA6, Rv0905, MTCY31.33 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-CoA_hydratase Enoyl-CoA hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.17 4.2.1.17] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-CoA_hydratase Enoyl-CoA hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.17 4.2.1.17] </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=5duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5duc OCA], [http://pdbe.org/5duc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5duc RCSB], [http://www.ebi.ac.uk/pdbsum/5duc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5duc ProSAT]</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=5duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5duc OCA], [http://pdbe.org/5duc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5duc RCSB], [http://www.ebi.ac.uk/pdbsum/5duc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5duc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 24:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Enoyl-CoA hydratase]]		[[Category: Enoyl-CoA hydratase]]
			[[Category: Large Structures]]
	[[Category: Besra, G S]]		[[Category: Besra, G S]]
	[[Category: Cox, J A.G]]		[[Category: Cox, J A.G]]

OCA at 08:18, 14 September 2016

2016-09-14T08:18:14Z

← Older revision		Revision as of 08:18, 14 September 2016
Line 1:		Line 1:

	==Crystal structure of M. tuberculosis EchA6 bound to ligand GSK951A==		==Crystal structure of M. tuberculosis EchA6 bound to ligand GSK951A==
	<StructureSection load='5duc' size='340' side='right' caption='[[5duc]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='5duc' size='340' side='right' caption='[[5duc]], [[Resolution\|resolution]] 2.70Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G51:(5R,7S)-N-(1,3-BENZODIOXOL-5-YLMETHYL)-5-(4-ETHYLPHENYL)-7-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE'>G51</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G51:(5R,7S)-N-(1,3-BENZODIOXOL-5-YLMETHYL)-5-(4-ETHYLPHENYL)-7-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE'>G51</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-CoA_hydratase Enoyl-CoA hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.17 4.2.1.17] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-CoA_hydratase Enoyl-CoA hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.17 4.2.1.17] </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=5duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5duc OCA], [http://pdbe.org/5duc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5duc RCSB], [http://www.ebi.ac.uk/pdbsum/5duc 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=5duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5duc OCA], [http://pdbe.org/5duc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5duc RCSB], [http://www.ebi.ac.uk/pdbsum/5duc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5duc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/ECHA6_MYCTU ECHA6_MYCTU]] Could possibly oxidize fatty acids using specific components.		[[http://www.uniprot.org/uniprot/ECHA6_MYCTU ECHA6_MYCTU]] Could possibly oxidize fatty acids using specific components.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Phenotypic screens for bactericidal compounds against drug-resistant tuberculosis are beginning to yield novel inhibitors. However, reliable target identification remains challenging. Here, we show that tetrahydropyrazo[1,5-a]pyrimidine-3-carboxamide (THPP) selectively pulls down EchA6 in a stereospecific manner, instead of the previously assigned target Mycobacterium tuberculosis MmpL3. While homologous to mammalian enoyl-coenzyme A (CoA) hydratases, EchA6 is non-catalytic yet essential and binds long-chain acyl-CoAs. THPP inhibitors compete with CoA-binding, suppress mycolic acid synthesis, and are bactericidal in a mouse model of chronic tuberculosis infection. A point mutation, W133A, abrogated THPP-binding and increased both the in vitro minimum inhibitory concentration and the in vivo effective dose 99 in mice. Surprisingly, EchA6 interacts with selected enzymes of fatty acid synthase II (FAS-II) in bacterial two-hybrid assays, suggesting essentiality may be linked to feeding long-chain fatty acids to FAS-II. Finally, our data show that spontaneous resistance-conferring mutations can potentially obscure the actual target or alternative targets of small molecule inhibitors.

			THPP target assignment reveals EchA6 as an essential fatty acid shuttle in mycobacteria.,Cox JA, Abrahams KA, Alemparte C, Ghidelli-Disse S, Rullas J, Angulo-Barturen I, Singh A, Gurcha SS, Nataraj V, Bethell S, Remuinan MJ, Encinas L, Jervis PJ, Cammack NC, Bhatt A, Kruse U, Bantscheff M, Futterer K, Barros D, Ballell L, Drewes G, Besra GS Nat Microbiol. 2016 Jan 18;1:15006. doi: 10.1038/nmicrobiol.2015.6. PMID:27571973<ref>PMID:27571973</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 5duc" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 17:22, 20 January 2016

2016-01-20T17:22:09Z

← Older revision		Revision as of 17:22, 20 January 2016
Line 1:		Line 1:
	'''~~Unreleased structure~~'''		==Crystal structure of M. tuberculosis EchA6 bound to ligand GSK951A==
			<StructureSection load='5duc' size='340' side='right' caption='[[5duc]], [[Resolution\|resolution]] 2.70Å' scene=''>
	~~The entry~~ 5duc is ~~ON HOLD until Paper Publication~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[5duc]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DUC FirstGlance]. <br>
	~~Authors~~: ~~Cox~~, J.A.G., ~~Besra~~, G.S., ~~Futterer, K~~.		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G51:(5R,7S)-N-(1,3-BENZODIOXOL-5-YLMETHYL)-5-(4-ETHYLPHENYL)-7-(TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE'>G51</scene></td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-CoA_hydratase Enoyl-CoA hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.17 4.2.1.17] </span></td></tr>
	~~Description~~: ~~Crystal structure of M~~. ~~tuberculosis EchA6 bound to ligand GSK951A~~		<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=5duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5duc OCA], [http://pdbe.org/5duc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5duc RCSB], [http://www.ebi.ac.uk/pdbsum/5duc PDBsum]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
	[[Category: Besra, G.S]]		== Function ==
	[[Category: Cox, J.A.G]]		[[http://www.uniprot.org/uniprot/ECHA6_MYCTU ECHA6_MYCTU]] Could possibly oxidize fatty acids using specific components.
			__TOC__
			</StructureSection>
			[[Category: Enoyl-CoA hydratase]]
			[[Category: Besra, G S]]
			[[Category: Cox, J A.G]]
	[[Category: Futterer, K]]		[[Category: Futterer, K]]
			[[Category: Enoyl-coa hydratase-like]]
			[[Category: Lipid binding protein]]
			[[Category: Lyase]]

OCA: Protected "5duc" [edit=sysop:move=sysop]

2015-09-30T13:32:41Z

Protected "5duc" [edit=sysop:move=sysop]

← Older revision	Revision as of 13:32, 30 September 2015
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5duc is ON HOLD until Paper Publication Authors: Cox, J.A.G., Besra, G.S., Futterer, K. Description: Crystal structure of M. tuberculosis EchA6 bou...

2015-09-30T13:32:39Z

New page: '''Unreleased structure''' The entry 5duc is ON HOLD until Paper Publication Authors: Cox, J.A.G., Besra, G.S., Futterer, K. Description: Crystal structure of M. tuberculosis EchA6 bou...

New page

'''Unreleased structure'''

The entry 5duc is ON HOLD until Paper Publication

Authors: Cox, J.A.G., Besra, G.S., Futterer, K.

Description: Crystal structure of M. tuberculosis EchA6 bound to ligand GSK951A
[[Category: Unreleased Structures]]
[[Category: Besra, G.S]]
[[Category: Cox, J.A.G]]
[[Category: Futterer, K]]