5ocj - Revision history

OCA at 09:39, 6 December 2023

2023-12-06T09:39:57Z

←Older revision		Revision as of 09:39, 6 December 2023
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	==Crystal structure of Ag85C bound to cyclophostin 8beta inhibitor==		==Crystal structure of Ag85C bound to cyclophostin 8beta inhibitor==
-	<StructureSection load='5ocj' size='340' side='right' caption='[[5ocj]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='5ocj' size='340' side='right'caption='[[5ocj]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ocj]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Myctu Myctu~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OCJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5OCJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ocj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OCJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OCJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9SW:methoxy-[(3~{R})-3-[(2~{R})-1-methoxy-1,3-bis(oxidanylidene)butan-2-yl]pentadecyl]phosphinic+acid'>9SW</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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]] 1.8Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">fbpC, mpt45, Rv0129c, MTCI5.03c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9SW:methoxy-[(3~{R})-3-[(2~{R})-1-methoxy-1,3-bis(oxidanylidene)butan-2-yl]pentadecyl]phosphinic+acid'>9SW</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></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=5ocj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ocj OCA], [~~http~~://pdbe.org/5ocj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ocj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ocj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ocj 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=5ocj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ocj OCA], [https://pdbe.org/5ocj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ocj RCSB], [https://www.ebi.ac.uk/pdbsum/5ocj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ocj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/A85C_MYCTU A85C_MYCTU]] The antigen 85 proteins (FbpA, FbpB, FbpC) are responsible for the high affinity of mycobacteria to fibronectin, a large adhesive glycoprotein, which facilitates the attachment of M.tuberculosis to murine alveolar macrophages (AMs). They also help to maintain the integrity of the cell wall by catalyzing the transfer of mycolic acids to cell wall arabinogalactan and through the synthesis of alpha,alpha-trehalose dimycolate (TDM, cord factor). They catalyze the transfer of a mycoloyl residue from one molecule of alpha,alpha-trehalose monomycolate (TMM) to another TMM, leading to the formation of TDM.<ref>PMID:1830294</ref> <ref>PMID:9162010</ref>	+	[https://www.uniprot.org/uniprot/A85C_MYCTU A85C_MYCTU] The antigen 85 proteins (FbpA, FbpB, FbpC) are responsible for the high affinity of mycobacteria to fibronectin, a large adhesive glycoprotein, which facilitates the attachment of M.tuberculosis to murine alveolar macrophages (AMs). They also help to maintain the integrity of the cell wall by catalyzing the transfer of mycolic acids to cell wall arabinogalactan and through the synthesis of alpha,alpha-trehalose dimycolate (TDM, cord factor). They catalyze the transfer of a mycoloyl residue from one molecule of alpha,alpha-trehalose monomycolate (TMM) to another TMM, leading to the formation of TDM.<ref>PMID:1830294</ref> <ref>PMID:9162010</ref>
	<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 5ocj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5ocj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antigen 85 3D structures\|Antigen 85 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Myctu~~]]	+	[[Category: Large Structures]]
-	[[Category: Blaise, M]]	+	[[Category: Mycobacterium tuberculosis H37Rv]]
-	[[Category: Canaan, S]]	+	[[Category: Blaise M]]
-	[[Category: Cavalier~~, J F~~]]	+	[[Category: Canaan S]]
-	[[Category: Kremer, L]]	+	[[Category: Cavalier JF]]
-	[[Category: Nguyen~~, P C~~]]	+	[[Category: Kremer L]]
-	[[Category: Richard, M]]	+	[[Category: Nguyen PC]]
-	[[Category: Spilling~~, C D~~]]	+	[[Category: Richard M]]
-	[[Category: Viljoen, A]]	+	[[Category: Spilling CD]]
-	~~[[Category: Ag85c]]~~	+	[[Category: Viljoen A]]
-	~~[[Category: Mycolicate]]~~	+
-	~~[[Category: Mycomembrane]]~~	+
-	~~[[Category: Tdm]]~~	+
-	~~[[Category: Tmm]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:46, 22 February 2018

2018-02-22T07:46:25Z

←Older revision		Revision as of 07:46, 22 February 2018
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	<StructureSection load='5ocj' size='340' side='right' caption='[[5ocj]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='5ocj' size='340' side='right' caption='[[5ocj]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ocj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OCJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OCJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ocj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OCJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OCJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9SW:methoxy-[(3~{R})-3-[(2~{R})-1-methoxy-1,3-bis(oxidanylidene)butan-2-yl]pentadecyl]phosphinic+acid'>9SW</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9SW:methoxy-[(3~{R})-3-[(2~{R})-1-methoxy-1,3-bis(oxidanylidene)butan-2-yl]pentadecyl]phosphinic+acid'>9SW</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">fbpC, mpt45, Rv0129c, MTCI5.03c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=5ocj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ocj OCA], [http://pdbe.org/5ocj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ocj RCSB], [http://www.ebi.ac.uk/pdbsum/5ocj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ocj 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=5ocj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ocj OCA], [http://pdbe.org/5ocj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ocj RCSB], [http://www.ebi.ac.uk/pdbsum/5ocj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ocj ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Myctu]]
	[[Category: Blaise, M]]		[[Category: Blaise, M]]
	[[Category: Canaan, S]]		[[Category: Canaan, S]]

OCA at 18:22, 24 January 2018

2018-01-24T18:22:56Z

←Older revision		Revision as of 18:22, 24 January 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5ocj is ~~ON HOLD~~	+	==Crystal structure of Ag85C bound to cyclophostin 8beta inhibitor==
		+	<StructureSection load='5ocj' size='340' side='right' caption='[[5ocj]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5ocj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OCJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OCJ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9SW:methoxy-[(3~{R})-3-[(2~{R})-1-methoxy-1,3-bis(oxidanylidene)butan-2-yl]pentadecyl]phosphinic+acid'>9SW</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></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=5ocj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ocj OCA], [http://pdbe.org/5ocj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ocj RCSB], [http://www.ebi.ac.uk/pdbsum/5ocj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ocj ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/A85C_MYCTU A85C_MYCTU]] The antigen 85 proteins (FbpA, FbpB, FbpC) are responsible for the high affinity of mycobacteria to fibronectin, a large adhesive glycoprotein, which facilitates the attachment of M.tuberculosis to murine alveolar macrophages (AMs). They also help to maintain the integrity of the cell wall by catalyzing the transfer of mycolic acids to cell wall arabinogalactan and through the synthesis of alpha,alpha-trehalose dimycolate (TDM, cord factor). They catalyze the transfer of a mycoloyl residue from one molecule of alpha,alpha-trehalose monomycolate (TMM) to another TMM, leading to the formation of TDM.<ref>PMID:1830294</ref> <ref>PMID:9162010</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	An increasing prevalence of cases of drug-resistant tuberculosis requires the development of more efficacious chemotherapies. We previously reported the discovery of a new class of Cyclipostins and Cyclophostin (CyC) analogs exhibiting potent activity against Mycobacterium tuberculosis both in vitro and in infected macrophages. Competitive labeling/enrichment assays combined with MS have identified several serine or cysteine enzymes in lipid and cell wall metabolism as putative targets of these CyC compounds. These targets included members of the antigen 85 (Ag85) complex (i.e. Ag85A, Ag85B, and Ag85C), responsible for biosynthesis of trehalose dimycolate (TDM) and mycolylation of arabinogalactan. Herein, we used biochemical and structural approaches to validate the Ag85 complex as a pharmacological target of the CyC analogs. We found that CyC7beta, CyC8beta, and CyC17 bind covalently to the catalytic Ser124 residue in Ag85C, inhibit mycolyltransferase activity, i.e. the transfer of a fatty acid molecule onto trehalose, and reduce triacylglycerol synthase activity, a property previously attributed to Ag85A. Supporting these results, an X-ray structure of Ag85C in complex with CyC8beta disclosed that this inhibitor occupies Ag85C's substrate-binding pocket. Importantly, metabolic labeling of M. tuberculosis cultures revealed that the CyC compounds impair both TDM synthesis and mycolylation of arabinogalactan. Overall, our study provides compelling evidence that CyC analogs can inhibit the activity of the Ag85 complex in vitro and in mycobacteria, opening the door to a new strategy for inhibiting Ag85. The high-resolution crystal structure obtained will further guide the rational optimization of new CyC scaffolds with greater specificity and potency against M. tuberculosis.

-	~~Authors~~:	+	Cyclipostins and Cyclophostin analogs inhibit the antigen 85C from Mycobacterium tuberculosis both in vitro and in vivo.,Viljoen A, Richard M, Nguyen PC, Fourquet P, Camoin L, Paudal RR, Gnawali GR, Spilling CD, Cavalier JF, Canaan S, Blaise M, Kremer L J Biol Chem. 2018 Jan 4. pii: RA117.000760. doi: 10.1074/jbc.RA117.000760. PMID:29301937<ref>PMID:29301937</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5ocj" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Blaise, M]]
		+	[[Category: Canaan, S]]
		+	[[Category: Cavalier, J F]]
		+	[[Category: Kremer, L]]
		+	[[Category: Nguyen, P C]]
		+	[[Category: Richard, M]]
		+	[[Category: Spilling, C D]]
		+	[[Category: Viljoen, A]]
		+	[[Category: Ag85c]]
		+	[[Category: Mycolicate]]
		+	[[Category: Mycomembrane]]
		+	[[Category: Tdm]]
		+	[[Category: Tmm]]
		+	[[Category: Transferase]]

OCA at 05:28, 17 January 2018

2018-01-17T05:28:48Z

←Older revision		Revision as of 05:28, 17 January 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5ocj is ON HOLD ~~until Paper Publication~~	+	The entry 5ocj is ON HOLD

	Authors:		Authors:

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

2017-09-27T12:16:41Z

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

←Older revision

Revision as of 12:16, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5ocj is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

2017-09-27T12:16:40Z

New page: '''Unreleased structure''' The entry 5ocj is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5ocj is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]