6th2 - Revision history

OCA at 13:02, 24 January 2024

OCA — Wed, 24 Jan 2024 13:02:12 GMT

←Older revision		Revision as of 13:02, 24 January 2024
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	<StructureSection load='6th2' size='340' side='right'caption='[[6th2]], [[Resolution\|resolution]] 1.84Å' scene=''>		<StructureSection load='6th2' size='340' side='right'caption='[[6th2]], [[Resolution\|resolution]] 1.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6th2]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Mycs2 Mycs2~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TH2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6TH2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6th2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TH2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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]] 1.844Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">coaBC, MSMEG_3054 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></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=6th2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6th2 OCA], [~~http~~://pdbe.org/6th2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6th2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6th2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6th2 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=6th2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6th2 OCA], [https://pdbe.org/6th2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6th2 RCSB], [https://www.ebi.ac.uk/pdbsum/6th2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6th2 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/COABC_MYCS2 COABC_MYCS2] Catalyzes two sequential steps in the biosynthesis of coenzyme A. In the first step cysteine is conjugated to 4'-phosphopantothenate to form 4-phosphopantothenoylcysteine. In the second step the latter compound is decarboxylated to form 4'-phosphopantotheine.[HAMAP-Rule:MF_02225]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Mycs2~~]]	+	[[Category: Mycolicibacterium smegmatis MC2 155]]
-	[[Category: Blaszczyk, M]]	+	[[Category: Blaszczyk M]]
-	[[Category: Blundell~~, T L~~]]	+	[[Category: Blundell TL]]
-	[[Category: Bryant, O]]	+	[[Category: Bryant O]]
-	[[Category: Cory-Wright, J]]	+	[[Category: Cory-Wright J]]
-	[[Category: Mendes, V]]	+	[[Category: Mendes V]]
-	~~[[Category: Bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate-cysteine ligase]]~~	+
-	~~[[Category: Coabc]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Phosphopantothenate-cysteine ligase]]~~	+
-	~~[[Category: Phosphopantothenoylcysteine decarboxylase]]~~	+
-	~~[[Category: Phosphopantothenoylcysteine synthetase~~]]	+

OCA at 08:21, 20 January 2021

OCA — Wed, 20 Jan 2021 08:21:10 GMT

←Older revision		Revision as of 08:21, 20 January 2021
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	==Crystal structure of Mycobacterium smegmatis CoaB in complex with CTP==		==Crystal structure of Mycobacterium smegmatis CoaB in complex with CTP==
-	<StructureSection load='6th2' size='340' side='right'caption='[[6th2]]' scene=''>	+	<StructureSection load='6th2' size='340' side='right'caption='[[6th2]], [[Resolution\|resolution]] 1.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TH2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TH2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6th2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TH2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TH2 FirstGlance]. <br>
-	</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=6th2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6th2 OCA], [http://pdbe.org/6th2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6th2 RCSB], [http://www.ebi.ac.uk/pdbsum/6th2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6th2 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">coaBC, MSMEG_3054 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</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=6th2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6th2 OCA], [http://pdbe.org/6th2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6th2 RCSB], [http://www.ebi.ac.uk/pdbsum/6th2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6th2 ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Coenzyme A (CoA) is a fundamental co-factor for all life, involved in numerous metabolic pathways and cellular processes, and its biosynthetic pathway has raised substantial interest as a drug target against multiple pathogens including Mycobacterium tuberculosis. The biosynthesis of CoA is performed in five steps, with the second and third steps being catalysed in the vast majority of prokaryotes, including M. tuberculosis, by a single bifunctional protein, CoaBC. Depletion of CoaBC was found to be bactericidal in M. tuberculosis. Here we report the first structure of a full-length CoaBC, from the model organism Mycobacterium smegmatis, describe how it is organised as a dodecamer and regulated by CoA thioesters. A high-throughput biochemical screen focusing on CoaB identified two inhibitors with different chemical scaffolds. Hit expansion led to the discovery of potent and selective inhibitors of M. tuberculosis CoaB, which we show to bind to a cryptic allosteric site within CoaB.
		+
		+	Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site.,Mendes V, Green SR, Evans JC, Hess J, Blaszczyk M, Spry C, Bryant O, Cory-Wright J, Chan DS, Torres PHM, Wang Z, Nahiyaan N, O'Neill S, Damerow S, Post J, Bayliss T, Lynch SL, Coyne AG, Ray PC, Abell C, Rhee KY, Boshoff HIM, Barry CE 3rd, Mizrahi V, Wyatt PG, Blundell TL Nat Commun. 2021 Jan 8;12(1):143. doi: 10.1038/s41467-020-20224-x. PMID:33420031<ref>PMID:33420031</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6th2" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Blaszczyk M]]	+	[[Category: Mycs2]]
-	[[Category: Blundell TL]]	+	[[Category: Blaszczyk, M]]
-	[[Category: Bryant O]]	+	[[Category: Blundell, T L]]
-	[[Category: Cory-Wright J]]	+	[[Category: Bryant, O]]
-	[[Category: Mendes V]]	+	[[Category: Cory-Wright, J]]
		+	[[Category: Mendes, V]]
		+	[[Category: Bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate-cysteine ligase]]
		+	[[Category: Coabc]]
		+	[[Category: Ligase]]
		+	[[Category: Phosphopantothenate-cysteine ligase]]
		+	[[Category: Phosphopantothenoylcysteine decarboxylase]]
		+	[[Category: Phosphopantothenoylcysteine synthetase]]

OCA at 06:53, 25 November 2020

OCA — Wed, 25 Nov 2020 06:53:15 GMT

←Older revision		Revision as of 06:53, 25 November 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6th2 ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of Mycobacterium smegmatis CoaB in complex with CTP==
-		+	<StructureSection load='6th2' size='340' side='right'caption='[[6th2]]' scene=''>
-	~~Authors~~: ~~Mendes, V~~.~~, Blaszczyk, M~~.~~, Bryant, O~~., ~~Cory~~-~~Wright~~, J., ~~Blundell~~, T.L.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TH2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TH2 FirstGlance]. <br>
-	~~Description: Crystal structure of Mycobacterium smegmatis CoaB in complex with CTP~~	+	</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=6th2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6th2 OCA], [http://pdbe.org/6th2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6th2 RCSB], [http://www.ebi.ac.uk/pdbsum/6th2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6th2 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Blundell, T.L~~]]	+	__TOC__
-	[[Category: ~~Mendes, V~~]]	+	</StructureSection>
-	[[Category: ~~Cory-Wright, J~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Blaszczyk, M~~]]	+	[[Category: Blaszczyk M]]
-	[[Category: ~~Bryant, O~~]]	+	[[Category: Blundell TL]]
		+	[[Category: Bryant O]]
		+	[[Category: Cory-Wright J]]
		+	[[Category: Mendes V]]

OCA: Protected "6th2" [edit=sysop:move=sysop]

OCA — Wed, 27 Nov 2019 05:16:18 GMT

Protected "6th2" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:16, 27 November 2019

OCA: New page: '''Unreleased structure''' The entry 6th2 is ON HOLD until Paper Publication Authors: Mendes, V., Blaszczyk, M., Bryant, O., Cory-Wright, J., Blundell, T.L. Description: Crystal struct...

OCA — Wed, 27 Nov 2019 05:16:17 GMT

New page: '''Unreleased structure''' The entry 6th2 is ON HOLD until Paper Publication Authors: Mendes, V., Blaszczyk, M., Bryant, O., Cory-Wright, J., Blundell, T.L. Description: Crystal struct...

New page

'''Unreleased structure'''

The entry 6th2 is ON HOLD until Paper Publication

Authors: Mendes, V., Blaszczyk, M., Bryant, O., Cory-Wright, J., Blundell, T.L.

Description: Crystal structure of Mycobacterium smegmatis CoaB in complex with CTP
[[Category: Unreleased Structures]]
[[Category: Blundell, T.L]]
[[Category: Mendes, V]]
[[Category: Cory-Wright, J]]
[[Category: Blaszczyk, M]]
[[Category: Bryant, O]]