8a76 - Revision history

OCA at 13:36, 1 February 2024

2024-02-01T13:36:45Z

← Older revision		Revision as of 13:36, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8a76]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A76 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A76 FirstGlance]. <br>		<table><tr><td colspan='2'>[[8a76]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A76 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A76 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=L82:(2~{S})-2-[bis(pyridin-2-ylmethyl)amino]-5-(3-phenyl-5-sulfanylidene-1~{H}-1,2,4-triazol-4-yl)pentanoic+acid'>L82</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.5Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=L82:(2~{S})-2-[bis(pyridin-2-ylmethyl)amino]-5-(3-phenyl-5-sulfanylidene-1~{H}-1,2,4-triazol-4-yl)pentanoic+acid'>L82</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8a76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a76 OCA], [https://pdbe.org/8a76 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a76 RCSB], [https://www.ebi.ac.uk/pdbsum/8a76 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a76 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=8a76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a76 OCA], [https://pdbe.org/8a76 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a76 RCSB], [https://www.ebi.ac.uk/pdbsum/8a76 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a76 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:08, 14 December 2022

2022-12-14T10:08:21Z

← Older revision		Revision as of 10:08, 14 December 2022
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	~~'''Unreleased structure'''~~

	~~The entry~~ 8a76 is ~~ON HOLD until Paper~~ Publication		==Metallo-beta-lactamase NDM-1 in complex with 1,2,4-Triazole-3-thione compound 26==
			<StructureSection load='8a76' size='340' side='right'caption='[[8a76]], [[Resolution\|resolution]] 1.50Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[8a76]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A76 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A76 FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=L82:(2~{S})-2-[bis(pyridin-2-ylmethyl)amino]-5-(3-phenyl-5-sulfanylidene-1~{H}-1,2,4-triazol-4-yl)pentanoic+acid'>L82</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8a76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a76 OCA], [https://pdbe.org/8a76 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a76 RCSB], [https://www.ebi.ac.uk/pdbsum/8a76 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a76 ProSAT]</span></td></tr>
			</table>
			== Function ==
			[https://www.uniprot.org/uniprot/M4JT39_PSEAI M4JT39_PSEAI]
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Metallo-beta-lactamases (MBLs) contribute to the resistance of Gram-negative bacteria to carbapenems, last-resort antibiotics at hospital, and MBL inhibitors are urgently needed to preserve these important antibacterial drugs. Here, we describe a series of 1,2,4-triazole-3-thione-based inhibitors displaying an alpha-amino acid substituent, which amine was mono- or disubstituted by (hetero)aryl groups. Compounds disubstituted by certain nitrogen-containing heterocycles showed submicromolar activities against VIM-type enzymes and strong NDM-1 inhibition (K(i) = 10-30 nM). Equilibrium dialysis, native mass spectrometry, isothermal calorimetry (ITC), and X-ray crystallography showed that the compounds inhibited both VIM-2 and NDM-1 at least partially by stripping the catalytic zinc ions. These inhibitors also displayed a very potent synergistic activity with meropenem (16- to 1000-fold minimum inhibitory concentration (MIC) reduction) against VIM-type- and NDM-1-producing ultraresistant clinical isolates, including Enterobacterales and Pseudomonas aeruginosa. Furthermore, selected compounds exhibited no or moderate toxicity toward HeLa cells, favorable absorption, distribution, metabolism, excretion (ADME) properties, and no or modest inhibition of several mammalian metalloenzymes.

	~~Authors:~~ Vascon, F., ~~Legru~~, A., ~~Hernandez~~, J.F., Cendron, L.		Optimization of 1,2,4-Triazole-3-thiones toward Broad-Spectrum Metallo-beta-lactamase Inhibitors Showing Potent Synergistic Activity on VIM- and NDM-1-Producing Clinical Isolates.,Legru A, Verdirosa F, Vo-Hoang Y, Tassone G, Vascon F, Thomas CA, Sannio F, Corsica G, Benvenuti M, Feller G, Coulon R, Marcoccia F, Devente SR, Bouajila E, Piveteau C, Leroux F, Deprez-Poulain R, Deprez B, Licznar-Fajardo P, Crowder MW, Cendron L, Pozzi C, Mangani S, Docquier JD, Hernandez JF, Gavara L J Med Chem. 2022 Nov 30. doi: 10.1021/acs.jmedchem.2c01257. PMID:36450011<ref>PMID:36450011</ref>

	~~Description: Metallo-beta-lactamase NDM-1 in complex with 1~~,~~2,4~~-~~Triazole~~-~~3-thione compound 26~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased~~ Structures]]		</div>
	[[Category: ~~Hernandez, J.F~~]]		<div class="pdbe-citations 8a76" style="background-color:#fffaf0;"></div>
	[[Category: Cendron, L]]		== References ==
	[[Category: Legru, A]]		<references/>
	[[Category: Vascon, F]]		__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Pseudomonas aeruginosa]]
			[[Category: Cendron L]]
			[[Category: Hernandez JF]]
			[[Category: Legru A]]
			[[Category: Vascon F]]

OCA at 16:31, 27 July 2022

2022-07-27T16:31:49Z

← Older revision		Revision as of 16:31, 27 July 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8a76 is ON HOLD		The entry 8a76 is ON HOLD until Paper Publication

	Authors: Vascon, F., Legru, A., Hernandez, J.F., Cendron, L.		Authors: Vascon, F., Legru, A., Hernandez, J.F., Cendron, L.

OCA: Protected "8a76" [edit=sysop:move=sysop]

2022-06-29T06:21:42Z

Protected "8a76" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:21, 29 June 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8a76 is ON HOLD Authors: Vascon, F., Legru, A., Hernandez, J.F., Cendron, L. Description: Metallo-beta-lactamase NDM-1 in complex with 1,2,4-Triazo...

2022-06-29T06:21:41Z

New page: '''Unreleased structure''' The entry 8a76 is ON HOLD Authors: Vascon, F., Legru, A., Hernandez, J.F., Cendron, L. Description: Metallo-beta-lactamase NDM-1 in complex with 1,2,4-Triazo...

New page

'''Unreleased structure'''

The entry 8a76 is ON HOLD

Authors: Vascon, F., Legru, A., Hernandez, J.F., Cendron, L.

Description: Metallo-beta-lactamase NDM-1 in complex with 1,2,4-Triazole-3-thione compound 26
[[Category: Unreleased Structures]]
[[Category: Hernandez, J.F]]
[[Category: Cendron, L]]
[[Category: Legru, A]]
[[Category: Vascon, F]]