7q2g - Revision history

OCA at 13:12, 1 February 2024

OCA — Thu, 01 Feb 2024 13:12:54 GMT

←Older revision		Revision as of 13:12, 1 February 2024
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	==mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT726==		==mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT726==
-	<StructureSection load='7q2g' size='340' side='right'caption='[[7q2g]]' scene=''>	+	<StructureSection load='7q2g' size='340' side='right'caption='[[7q2g]], [[Resolution\|resolution]] 2.00Å' 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=7Q2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q2G FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7q2g]] is a 1 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=7Q2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q2G FirstGlance]. <br>
-	</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=7q2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q2g OCA], [https://pdbe.org/7q2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q2g RCSB], [https://www.ebi.ac.uk/pdbsum/7q2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q2g ProSAT]</span></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]] 2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8MJ:8-oxidanylquinoline-2-carbaldehyde'>8MJ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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'>[https://proteopedia.org/fgij/fg.htm?mol=7q2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q2g OCA], [https://pdbe.org/7q2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q2g RCSB], [https://www.ebi.ac.uk/pdbsum/7q2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q2g ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/MMAA4_MYCTU MMAA4_MYCTU] Involved in the biosynthesis of hydroxymycolate, a common precursor of oxygenated mycolic acids (methoxy-mycolate and keto-mycolate). Probably transfers a methyl group from the S-adenosylmethionine (SAM) cofactor and, subsequently or simultaneously, a water molecule onto the double bound of ethylene substrates, leading to the formation of the hydroxylated product at the distal position. Involved in the activation of the antitubercular drug thiacetazone (TAC).<ref>PMID:10844652</ref> <ref>PMID:12473649</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The mycolic acid biosynthetic pathway represents a promising source of pharmacological targets in the fight against tuberculosis. In Mycobacterium tuberculosis, mycolic acids are subject to specific chemical modifications introduced by a set of eight S-adenosylmethionine dependent methyltransferases. Among these, Hma (MmaA4) is responsible for the introduction of oxygenated modifications. Crystallographic screening of a library of fragments allowed the identification of seven ligands of Hma. Two mutually exclusive binding modes were identified, depending on the conformation of residues 147-154. These residues are disordered in apo-Hma but fold upon binding of the S-adenosylmethionine (SAM) cofactor as well as of analogues, resulting in the formation of the short eta1-helix. One of the observed conformations would be incompatible with the presence of the cofactor, suggesting that allosteric inhibitors could be designed against Hma. Chimeric compounds were designed by fusing some of the bound fragments, and the relative binding affinities of initial fragments and evolved compounds were investigated using molecular dynamics simulation and generalised Born and Poisson-Boltzmann calculations coupled to the surface area continuum solvation method. Molecular dynamics simulations were also performed on apo-Hma to assess the structural plasticity of the unliganded protein. Our results indicate a significant improvement in the binding properties of the designed compounds, suggesting that they could be further optimised to inhibit Hma activity.
		+
		+	Fragment-Based Ligand Discovery Applied to the Mycolic Acid Methyltransferase Hma (MmaA4) from Mycobacterium tuberculosis: A Crystallographic and Molecular Modelling Study.,Galy R, Ballereau S, Genisson Y, Mourey L, Plaquevent JC, Maveyraud L Pharmaceuticals (Basel). 2021 Dec 8;14(12). pii: ph14121282. doi:, 10.3390/ph14121282. PMID:34959681<ref>PMID:34959681</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7q2g" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Mycobacterium tuberculosis H37Rv]]
	[[Category: Galy R]]		[[Category: Galy R]]
	[[Category: Maveyraud L]]		[[Category: Maveyraud L]]
	[[Category: Mourey L]]		[[Category: Mourey L]]

OCA at 07:02, 2 February 2022

OCA — Wed, 02 Feb 2022 07:02:21 GMT

←Older revision		Revision as of 07:02, 2 February 2022
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-	'''Unreleased structure'''

-	~~The entry 7q2g is ON HOLD until Paper Publication~~	+	==mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT726==
-		+	<StructureSection load='7q2g' size='340' side='right'caption='[[7q2g]]' scene=''>
-	~~Authors: Maveyraud, L., Galy, R., Mourey, L.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q2G FirstGlance]. <br>
-	~~Description:~~ mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT726	+	</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=7q2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q2g OCA], [https://pdbe.org/7q2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q2g RCSB], [https://www.ebi.ac.uk/pdbsum/7q2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q2g ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Mourey, L~~]]	+	__TOC__
-	[[Category: Maveyraud, L]]	+	</StructureSection>
-	[[Category: ~~Galy, R~~]]	+	[[Category: Large Structures]]
		+	[[Category: Galy R]]
		+	[[Category: Maveyraud L]]
		+	[[Category: Mourey L]]

OCA at 05:01, 1 December 2021

OCA — Wed, 01 Dec 2021 05:01:42 GMT

←Older revision		Revision as of 05:01, 1 December 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7q2g is ON HOLD	+	The entry 7q2g is ON HOLD until Paper Publication

	Authors: Maveyraud, L., Galy, R., Mourey, L.		Authors: Maveyraud, L., Galy, R., Mourey, L.

OCA: Protected "7q2g" [edit=sysop:move=sysop]

OCA — Wed, 03 Nov 2021 12:44:29 GMT

Protected "7q2g" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:44, 3 November 2021

OCA: New page: '''Unreleased structure''' The entry 7q2g is ON HOLD Authors: Maveyraud, L., Galy, R., Mourey, L. Description: mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculos...

OCA — Wed, 03 Nov 2021 12:44:28 GMT

New page: '''Unreleased structure''' The entry 7q2g is ON HOLD Authors: Maveyraud, L., Galy, R., Mourey, L. Description: mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculos...

New page

'''Unreleased structure'''

The entry 7q2g is ON HOLD

Authors: Maveyraud, L., Galy, R., Mourey, L.

Description: mycolic acid methyltransferase Hma (MmaA4) from Mycobac-terium tuberculosis in complex with ZT726
[[Category: Unreleased Structures]]
[[Category: Mourey, L]]
[[Category: Maveyraud, L]]
[[Category: Galy, R]]