6s7u - Revision history

OCA at 12:36, 24 January 2024

2024-01-24T12:36:57Z

←Older revision		Revision as of 12:36, 24 January 2024
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	<StructureSection load='6s7u' size='340' side='right'caption='[[6s7u]], [[Resolution\|resolution]] 1.48Å' scene=''>		<StructureSection load='6s7u' size='340' side='right'caption='[[6s7u]], [[Resolution\|resolution]] 1.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6s7u]] is a 4 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=6S7U OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6S7U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6s7u]] is a 4 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=6S7U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S7U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=KZK:~{N}-[5-(azepan-1-ylsulfonyl)-2-methoxy-phenyl]-2-(1~{H}-indol-3-yl)ethanamide'>KZK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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">fum, fumC, DSI35_09545, ERS007663_02818, ERS007679_02635, ERS007688_02307, ERS007722_03256, ERS023446_00966, ERS024276_01230, ERS027646_00759, ERS027653_00188, ERS027654_00515, ERS027659_00384, ERS027661_00671, ERS027666_02275, ERS124361_03161, SAMEA2682864_03539, SAMEA2683035_02636 ([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=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=KZK:~{N}-[5-(azepan-1-ylsulfonyl)-2-methoxy-phenyl]-2-(1~{H}-indol-3-yl)ethanamide'>KZK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fumarate_hydratase Fumarate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.2 4.2.1.2] </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=6s7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s7u OCA], [https://pdbe.org/6s7u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s7u RCSB], [https://www.ebi.ac.uk/pdbsum/6s7u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s7u ProSAT]</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=6s7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s7u OCA], [~~http~~://pdbe.org/6s7u PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6s7u RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6s7u PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6s7u ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~A0A045IXZ8_MYCTX A0A045IXZ8_MYCTX~~]~~] Involved in the TCA cycle.~~ Catalyzes the ~~stereospecific interconversion~~ of fumarate to L-malate.~~[HAMAP-Rule:MF_00743]~~	+	[https://www.uniprot.org/uniprot/FUMC_MYCTU FUMC_MYCTU] Catalyzes the reversible addition of water to fumarate to give L-malate.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6s7u" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6s7u" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Fumarase\|Fumarase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Fumarate hydratase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Abell, C]]	+	[[Category: Mycobacterium tuberculosis]]
-	[[Category: Barry~~, C E~~]]	+	[[Category: Abell C]]
-	[[Category: Boshoff~~, H I~~]]	+	[[Category: Barry CE]]
-	[[Category: Brear, P]]	+	[[Category: Boshoff HI]]
-	[[Category: Coyne~~, A G~~]]	+	[[Category: Brear P]]
-	[[Category: Fischer, G]]	+	[[Category: Coyne AG]]
-	[[Category: Kasbekar, M]]	+	[[Category: Fischer G]]
-	[[Category: Libardo~~, M D~~]]	+	[[Category: Kasbekar M]]
-	[[Category: Thomas~~, C J~~]]	+	[[Category: Libardo MD]]
-	[[Category: Whitehouse~~, A J]]~~	+	[[Category: Thomas CJ]]
-	~~[[Category: Fumarase]]~~	+	[[Category: Whitehouse AJ]]
-	~~[[Category: Lyase~~]]	+

OCA at 13:16, 25 December 2019

2019-12-25T13:16:49Z

←Older revision		Revision as of 13:16, 25 December 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6s7u is ~~ON HOLD until Paper~~ Publication	+	==Fumarate hydratase of Mycobacterium tuberculosis in complex with formate and allosteric modulator N-(5-(Azepan-1-ylsulfonyl)-2-methoxyphenyl)-2-(1H-indol-3-yl)acetamide==
		+	<StructureSection load='6s7u' size='340' side='right'caption='[[6s7u]], [[Resolution\|resolution]] 1.48Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6s7u]] is a 4 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=6S7U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S7U FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=KZK:~{N}-[5-(azepan-1-ylsulfonyl)-2-methoxy-phenyl]-2-(1~{H}-indol-3-yl)ethanamide'>KZK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">fum, fumC, DSI35_09545, ERS007663_02818, ERS007679_02635, ERS007688_02307, ERS007722_03256, ERS023446_00966, ERS024276_01230, ERS027646_00759, ERS027653_00188, ERS027654_00515, ERS027659_00384, ERS027661_00671, ERS027666_02275, ERS124361_03161, SAMEA2682864_03539, SAMEA2683035_02636 ([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/Fumarate_hydratase Fumarate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.2 4.2.1.2] </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=6s7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s7u OCA], [http://pdbe.org/6s7u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s7u RCSB], [http://www.ebi.ac.uk/pdbsum/6s7u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s7u ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/A0A045IXZ8_MYCTX A0A045IXZ8_MYCTX]] Involved in the TCA cycle. Catalyzes the stereospecific interconversion of fumarate to L-malate.[HAMAP-Rule:MF_00743]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	With the growing worldwide prevalence of antibiotic-resistant strains of tuberculosis (TB), new targets are urgently required for the development of treatments with novel modes of action. Fumarate hydratase (fumarase), a vulnerable component of the citric acid cycle in Mycobacterium tuberculosis (Mtb), is a metabolic target that could satisfy this unmet demand. A key challenge in the targeting of Mtb fumarase is its similarity to the human homolog, which shares an identical active site. A potential solution to this selectivity problem was previously found in a high-throughput screening hit that binds in a nonconserved allosteric site. In this work, a structure-activity relationship study was carried out with the determination of further structural biology on the lead series, affording derivatives with sub-micromolar inhibition. Further, the screening of this series against Mtb in vitro identified compounds with potent minimum inhibitory concentrations.

-	~~Authors:~~ Whitehouse~~, A.J.~~, Libardo~~, M.D.~~, Kasbekar, M., Brear~~, P.~~, Fischer, G., Thomas~~, C.J.~~, Barry, C.E.~~, Boshoff, H~~.I.~~, Coyne, A~~.G., ~~Abell, C~~.	+	Targeting of Fumarate Hydratase from Mycobacterium tuberculosis Using Allosteric Inhibitors with a Dimeric-Binding Mode.,Whitehouse AJ, Libardo MDJ, Kasbekar M, Brear PD, Fischer G, Thomas CJ, Barry CE 3rd, Boshoff HIM, Coyne AG, Abell C J Med Chem. 2019 Dec 12;62(23):10586-10604. doi: 10.1021/acs.jmedchem.9b01203., Epub 2019 Sep 27. PMID:31517489<ref>PMID:31517489</ref>

-	~~Description: Fumarate hydratase~~ of ~~Mycobacterium tuberculosis in complex with formate and allosteric modulator N~~-(5-~~(Azepan-1-ylsulfonyl)-2-methoxyphenyl)-2-(1H-indol-3-yl)acetamide~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	~~[[Category: Thomas, C.J]]~~	+	<div class="pdbe-citations 6s7u" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Kasbekar, M~~]]	+	== References ==
-	[[Category: ~~Fischer, G~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Fumarate hydratase]]
		+	[[Category: Large Structures]]
	[[Category: Abell, C]]		[[Category: Abell, C]]
		+	[[Category: Barry, C E]]
		+	[[Category: Boshoff, H I]]
	[[Category: Brear, P]]		[[Category: Brear, P]]
-	[[Category: ~~Whitehouse~~, A.J]]	+	[[Category: Coyne, A G]]
-	[[Category: ~~Coyne~~, A.G]]	+	[[Category: Fischer, G]]
-	[[Category: Libardo, M.D]]	+	[[Category: Kasbekar, M]]
-	[[Category: ~~Boshoff~~, ~~H.I~~]]	+	[[Category: Libardo, M D]]
-	[[Category: ~~Barry~~, ~~C.E~~]]	+	[[Category: Thomas, C J]]
		+	[[Category: Whitehouse, A J]]
		+	[[Category: Fumarase]]
		+	[[Category: Lyase]]

OCA: Protected "6s7u" [edit=sysop:move=sysop]

2019-07-17T09:15:51Z

Protected "6s7u" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:15, 17 July 2019

OCA: New page: '''Unreleased structure''' The entry 6s7u is ON HOLD until Paper Publication Authors: Whitehouse, A.J., Libardo, M.D., Kasbekar, M., Brear, P., Fischer, G., Thomas, C.J., Barry, C.E., B...

2019-07-17T09:15:49Z

New page: '''Unreleased structure''' The entry 6s7u is ON HOLD until Paper Publication Authors: Whitehouse, A.J., Libardo, M.D., Kasbekar, M., Brear, P., Fischer, G., Thomas, C.J., Barry, C.E., B...

New page

'''Unreleased structure'''

The entry 6s7u is ON HOLD until Paper Publication

Authors: Whitehouse, A.J., Libardo, M.D., Kasbekar, M., Brear, P., Fischer, G., Thomas, C.J., Barry, C.E., Boshoff, H.I., Coyne, A.G., Abell, C.

Description: Fumarate hydratase of Mycobacterium tuberculosis in complex with formate and allosteric modulator N-(5-(Azepan-1-ylsulfonyl)-2-methoxyphenyl)-2-(1H-indol-3-yl)acetamide
[[Category: Unreleased Structures]]
[[Category: Thomas, C.J]]
[[Category: Kasbekar, M]]
[[Category: Fischer, G]]
[[Category: Abell, C]]
[[Category: Brear, P]]
[[Category: Whitehouse, A.J]]
[[Category: Coyne, A.G]]
[[Category: Libardo, M.D]]
[[Category: Boshoff, H.I]]
[[Category: Barry, C.E]]