7u0m - Revision history

OCA at 17:09, 18 October 2023

OCA — Wed, 18 Oct 2023 17:09:57 GMT

←Older revision		Revision as of 17:09, 18 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7u0m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacteroides_abscessus Mycobacteroides abscessus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U0M FirstGlance]. <br>		<table><tr><td colspan='2'>[[7u0m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacteroides_abscessus Mycobacteroides abscessus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U0M FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3KY:6-[(4,4-DIMETHYLCYCLOHEXYL)METHYL]-4-HYDROXY-3-PHENYLPYRIDIN-2(1H)-ONE'>3KY</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 1.45Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3KY:6-[(4,4-DIMETHYLCYCLOHEXYL)METHYL]-4-HYDROXY-3-PHENYLPYRIDIN-2(1H)-ONE'>3KY</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=7u0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u0m OCA], [https://pdbe.org/7u0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u0m RCSB], [https://www.ebi.ac.uk/pdbsum/7u0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u0m 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=7u0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u0m OCA], [https://pdbe.org/7u0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u0m RCSB], [https://www.ebi.ac.uk/pdbsum/7u0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u0m ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 7u0m" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7u0m" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures\|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:25, 26 October 2022

OCA — Wed, 26 Oct 2022 06:25:52 GMT

←Older revision		Revision as of 06:25, 26 October 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7u0m is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of a enoyl-[acyl-carrier-protein] reductase (InhA) from Mycobacterium abscessus bound to NAD and NITD-916==
		+	<StructureSection load='7u0m' size='340' side='right'caption='[[7u0m]], [[Resolution\|resolution]] 1.45Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7u0m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacteroides_abscessus Mycobacteroides abscessus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U0M FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3KY:6-[(4,4-DIMETHYLCYCLOHEXYL)METHYL]-4-HYDROXY-3-PHENYLPYRIDIN-2(1H)-ONE'>3KY</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=7u0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u0m OCA], [https://pdbe.org/7u0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u0m RCSB], [https://www.ebi.ac.uk/pdbsum/7u0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u0m ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/B1MC30_MYCA9 B1MC30_MYCA9]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	There is an unmet medical need for effective treatments against Mycobacterium abscessus pulmonary infections, to which cystic fibrosis (CF) patients are particularly vulnerable. Recent studies showed that the antitubercular drug isoniazid is inactive against M. abscessus due to the incapacity of the catalase-peroxidase to convert the pro-drug into a reactive metabolite that inhibits the enoyl-ACP reductase InhA. To validate InhAMAB as a druggable target in M. abscessus, we assayed the activity of NITD-916, a 4-hydroxy-2-pyridone lead candidate initially described as a direct inhibitor of InhA that bypasses KatG bioactivation in Mycobacterium tuberculosis. The compound displayed low MIC values against rough and smooth clinical isolates in vitro and significantly reduced the bacterial burden inside human macrophages. Moreover, treatment with NITD-916 reduced the number and size of intracellular mycobacterial cords, regarded as markers of the severity of the infection. Importantly, NITD-916 significantly lowered the M. abscessus burden in CF-derived lung airway organoids. From a mechanistic perspective, NITD-916 abrogated de novo synthesis of mycolic acids and NITD-916-resistant spontaneous mutants harbored point mutations in InhAMAB at residue 96. That NITD-916 targets InhAMAB directly without activation requirements was confirmed genetically and by resolving the crystal structure of the protein in complex with NADH and NITD-916. These findings collectively indicate that InhAMAB is an attractive target to be exploited for future chemotherapeutic developments against this difficult-to-treat mycobacterium and highlight the potential of NITD-916 derivatives for further evaluation in preclinical settings.

-	~~Authors: Seattle Structural Genomics Center for Infectious Disease~~, ~~Seattle Structural Genomics Center for Infectious Disease (SSGCID)~~	+	Efficacy and Mode of Action of a Direct Inhibitor of Mycobacterium abscessus InhA.,Alcaraz M, Roquet-Baneres F, Leon-Icaza SA, Abendroth J, Boudehen YM, Cougoule C, Edwards TE, Kremer L ACS Infect Dis. 2022 Sep 15. doi: 10.1021/acsinfecdis.2c00314. PMID:36107992<ref>PMID:36107992</ref>

-	~~Description: Crystal structure of~~ a ~~enoyl~~-~~[acyl-carrier~~-~~protein] reductase (InhA) from Mycobacterium abscessus bound to NAD and NITD-916~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Seattle Structural Genomics Center For Infectious Disease, Seattle~~ Structural ~~Genomics Center For Infectious Disease (Ssgcid)~~]]	+	<div class="pdbe-citations 7u0m" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Mycobacteroides abscessus]]
		+	[[Category: Structural genomic]]

OCA at 09:47, 23 March 2022

OCA — Wed, 23 Mar 2022 09:47:29 GMT

←Older revision		Revision as of 09:47, 23 March 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7u0m is ON HOLD	+	The entry 7u0m is ON HOLD until Paper Publication

	Authors: Seattle Structural Genomics Center for Infectious Disease, Seattle Structural Genomics Center for Infectious Disease (SSGCID)		Authors: Seattle Structural Genomics Center for Infectious Disease, Seattle Structural Genomics Center for Infectious Disease (SSGCID)

OCA: Protected "7u0m" [edit=sysop:move=sysop]

OCA — Wed, 02 Mar 2022 05:06:22 GMT

Protected "7u0m" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:06, 2 March 2022

OCA: New page: '''Unreleased structure''' The entry 7u0m is ON HOLD Authors: Seattle Structural Genomics Center for Infectious Disease, Seattle Structural Genomics Center for Infectious Disease (SSGCI...

OCA — Wed, 02 Mar 2022 05:06:21 GMT

New page: '''Unreleased structure''' The entry 7u0m is ON HOLD Authors: Seattle Structural Genomics Center for Infectious Disease, Seattle Structural Genomics Center for Infectious Disease (SSGCI...

New page

'''Unreleased structure'''

The entry 7u0m is ON HOLD

Authors: Seattle Structural Genomics Center for Infectious Disease, Seattle Structural Genomics Center for Infectious Disease (SSGCID)

Description: Crystal structure of a enoyl-[acyl-carrier-protein] reductase (InhA) from Mycobacterium abscessus bound to NAD and NITD-916
[[Category: Unreleased Structures]]
[[Category: Seattle Structural Genomics Center For Infectious Disease, Seattle Structural Genomics Center For Infectious Disease (Ssgcid)]]