8a4m - Revision history

OCA at 08:08, 7 February 2024

2024-02-07T08:08:48Z

← Older revision		Revision as of 08:08, 7 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8a4m]] is a 1 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=8A4M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A4M FirstGlance]. <br>		<table><tr><td colspan='2'>[[8a4m]] is a 1 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=8A4M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A4M 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=L2R:(2~{S})-2-[bis(1~{H}-imidazol-4-ylmethyl)amino]-5-(3-phenyl-5-sulfanylidene-1~{H}-1,2,4-triazol-4-yl)pentanoic+acid'>L2R</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]] 1.98Å</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=L2R:(2~{S})-2-[bis(1~{H}-imidazol-4-ylmethyl)amino]-5-(3-phenyl-5-sulfanylidene-1~{H}-1,2,4-triazol-4-yl)pentanoic+acid'>L2R</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=8a4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a4m OCA], [https://pdbe.org/8a4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a4m RCSB], [https://www.ebi.ac.uk/pdbsum/8a4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a4m 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=8a4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a4m OCA], [https://pdbe.org/8a4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a4m RCSB], [https://www.ebi.ac.uk/pdbsum/8a4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a4m ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/B8QIQ9_PSEAI B8QIQ9_PSEAI]		[https://www.uniprot.org/uniprot/B8QIQ9_PSEAI B8QIQ9_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.

	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>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 8a4m" style="background-color:#fffaf0;"></div>~~
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 17:01, 26 April 2023

2023-04-26T17:01:53Z

← Older revision		Revision as of 17:01, 26 April 2023
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	~~'''Unreleased structure'''~~

	~~The entry~~ 8a4m is ~~ON HOLD until Paper~~ Publication		==Crystal structure of the VIM-2 acquired metallo-beta-Lactamase in complex with compound 8 (JMV-7061)==
			<StructureSection load='8a4m' size='340' side='right'caption='[[8a4m]], [[Resolution\|resolution]] 1.98Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[8a4m]] is a 1 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=8A4M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A4M 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=L2R:(2~{S})-2-[bis(1~{H}-imidazol-4-ylmethyl)amino]-5-(3-phenyl-5-sulfanylidene-1~{H}-1,2,4-triazol-4-yl)pentanoic+acid'>L2R</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=8a4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a4m OCA], [https://pdbe.org/8a4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a4m RCSB], [https://www.ebi.ac.uk/pdbsum/8a4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a4m ProSAT]</span></td></tr>
			</table>
			== Function ==
			[https://www.uniprot.org/uniprot/B8QIQ9_PSEAI B8QIQ9_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:~~ Tassone, G., Benvenuti, M., ~~Verdirosa~~, F., ~~Corsica~~, G., ~~Sannio~~, F., ~~Docquier~~, ~~J.D.~~, Pozzi, C., Mangani, S.		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: Crystal structure~~ of the ~~VIM~~-~~2 acquired metallo~~-~~beta-Lactamase in complex with compound 8 (JMV-7061)~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased~~ Structures]]		</div>
	[[Category: ~~Sannio, F~~]]		<div class="pdbe-citations 8a4m" style="background-color:#fffaf0;"></div>
	[[Category: Benvenuti, M]]		== References ==
	[[Category: Docquier~~, J.D~~]]		<references/>
	[[Category: ~~Tassone, G~~]]		__TOC__
	[[Category: Pozzi, C]]		</StructureSection>
	[[Category: ~~Verdirosa,~~ F]]		[[Category: Large Structures]]
	[[Category: ~~Mangani, S~~]]		[[Category: Pseudomonas aeruginosa]]
	[[Category: ~~Corsica, G~~]]		[[Category: Benvenuti M]]
			[[Category: Corsica G]]
			[[Category: Docquier JD]]
			[[Category: Mangani S]]
			[[Category: Pozzi C]]
			[[Category: Sannio F]]
			[[Category: Tassone G]]
			[[Category: Verdirosa F]]

OCA at 15:03, 6 July 2022

2022-07-06T15:03:57Z

← Older revision		Revision as of 15:03, 6 July 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8a4m is ON HOLD		The entry 8a4m is ON HOLD until Paper Publication

	Authors: Tassone, G., Benvenuti, M., Verdirosa, F., Corsica, G., Sannio, F., Docquier, J.D., Pozzi, C., Mangani, S.		Authors: Tassone, G., Benvenuti, M., Verdirosa, F., Corsica, G., Sannio, F., Docquier, J.D., Pozzi, C., Mangani, S.
Line 8:		Line 8:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Sannio, F]]		[[Category: Sannio, F]]
	~~[[Category: Verdirosa, F]]~~
	[[Category: Benvenuti, M]]		[[Category: Benvenuti, M]]
	~~[[Category: Mangani, S]]~~
	[[Category: Docquier, J.D]]		[[Category: Docquier, J.D]]
	~~[[Category: Corsica, G]]~~
	[[Category: Tassone, G]]		[[Category: Tassone, G]]
	[[Category: Pozzi, C]]		[[Category: Pozzi, C]]
			[[Category: Verdirosa, F]]
			[[Category: Mangani, S]]
			[[Category: Corsica, G]]

OCA: Protected "8a4m" [edit=sysop:move=sysop]

2022-06-22T07:19:40Z

Protected "8a4m" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:19, 22 June 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8a4m is ON HOLD Authors: Tassone, G., Benvenuti, M., Verdirosa, F., Corsica, G., Sannio, F., Docquier, J.D., Pozzi, C., Mangani, S. Description: Cr...

2022-06-22T07:19:39Z

New page: '''Unreleased structure''' The entry 8a4m is ON HOLD Authors: Tassone, G., Benvenuti, M., Verdirosa, F., Corsica, G., Sannio, F., Docquier, J.D., Pozzi, C., Mangani, S. Description: Cr...

New page

'''Unreleased structure'''

The entry 8a4m is ON HOLD

Authors: Tassone, G., Benvenuti, M., Verdirosa, F., Corsica, G., Sannio, F., Docquier, J.D., Pozzi, C., Mangani, S.

Description: Crystal structure of the VIM-2 acquired metallo-beta-Lactamase in complex with compound 8 (JMV-7061)
[[Category: Unreleased Structures]]
[[Category: Sannio, F]]
[[Category: Verdirosa, F]]
[[Category: Benvenuti, M]]
[[Category: Mangani, S]]
[[Category: Docquier, J.D]]
[[Category: Corsica, G]]
[[Category: Tassone, G]]
[[Category: Pozzi, C]]