6zyn - Revision history

OCA at 12:00, 1 February 2024

OCA — Thu, 01 Feb 2024 12:00:20 GMT

←Older revision		Revision as of 12:00, 1 February 2024
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	<StructureSection load='6zyn' size='340' side='right'caption='[[6zyn]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='6zyn' size='340' side='right'caption='[[6zyn]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6zyn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZYN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6zyn]] 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=6ZYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZYN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=QT2:(2~{S},4~{R})-2-ethoxycarbonyl-5,5-dimethyl-2-(sulfanylmethyl)-1,3-thiazolidine-4-carboxylic+acid'>QT2</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]] 1.4000138Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaVIM-2, bla vim-2, bla-VIM-2, blasVIM-2, blaVIM2, blm, VIM-2, vim-2, PAERUG_P32_London_17_VIM_2_10_11_06255 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=QT2:(2~{S},4~{R})-2-ethoxycarbonyl-5,5-dimethyl-2-(sulfanylmethyl)-1,3-thiazolidine-4-carboxylic+acid'>QT2</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=6zyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zyn OCA], [https://pdbe.org/6zyn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zyn RCSB], [https://www.ebi.ac.uk/pdbsum/6zyn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zyn 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=6zyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zyn OCA], [https://pdbe.org/6zyn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zyn RCSB], [https://www.ebi.ac.uk/pdbsum/6zyn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zyn ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q9K2N0_PSEAI Q9K2N0_PSEAI]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Hinchliffe, P~~]]	+	[[Category: Pseudomonas aeruginosa]]
-	[[Category: ~~Spencer, J~~]]	+	[[Category: Hinchliffe P]]
-	[[Category: ~~Antibiotic resistance]]~~	+	[[Category: Spencer J]]
-	~~[[Category: Antimicrobial protein]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Lactamase]]~~	+
-	~~[[Category: Zinc~~]]	+

OCA at 10:10, 7 July 2021

OCA — Wed, 07 Jul 2021 10:10:07 GMT

←Older revision		Revision as of 10:10, 7 July 2021
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	==Structure of VIM-2 with 2-Mercaptomethyl-thiazolidine L-anti-1b==		==Structure of VIM-2 with 2-Mercaptomethyl-thiazolidine L-anti-1b==
-	<StructureSection load='6zyn' size='340' side='right'caption='[[6zyn]]' scene=''>	+	<StructureSection load='6zyn' size='340' side='right'caption='[[6zyn]], [[Resolution\|resolution]] 1.40Å' 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=6ZYN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6ZYN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6zyn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZYN FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6zyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zyn OCA], [~~http~~://pdbe.org/6zyn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6zyn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6zyn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6zyn ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=QT2:(2~{S},4~{R})-2-ethoxycarbonyl-5,5-dimethyl-2-(sulfanylmethyl)-1,3-thiazolidine-4-carboxylic+acid'>QT2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaVIM-2, bla vim-2, bla-VIM-2, blasVIM-2, blaVIM2, blm, VIM-2, vim-2, PAERUG_P32_London_17_VIM_2_10_11_06255 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</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=6zyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zyn OCA], [https://pdbe.org/6zyn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zyn RCSB], [https://www.ebi.ac.uk/pdbsum/6zyn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zyn ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Infections caused by multidrug resistant (MDR) bacteria are a major public health threat. Carbapenems are among the most potent antimicrobial agents that are commercially available to treat MDR bacteria. Bacterial production of carbapenem-hydrolysing metallo-beta-lactamases (MBLs) challenges their safety and efficacy, with subclass B1 MBLs hydrolysing almost all beta-lactam antibiotics. MBL inhibitors would fulfil an urgent clinical need by prolonging the lifetime of these life-saving drugs. Here we report the synthesis and activity of a series of 2-mercaptomethyl-thiazolidines (MMTZs), designed to replicate MBL interactions with reaction intermediates or hydrolysis products. MMTZs are potent competitive inhibitors of B1 MBLs in vitro (e.g., K i = 0.44 muM vs. NDM-1). Crystal structures of MMTZ complexes reveal similar binding patterns to the most clinically important B1 MBLs (NDM-1, VIM-2 and IMP-1), contrasting with previously studied thiol-based MBL inhibitors, such as bisthiazolidines (BTZs) or captopril stereoisomers, which exhibit lower, more variable potencies and multiple binding modes. MMTZ binding involves thiol coordination to the Zn(ii) site and extensive hydrophobic interactions, burying the inhibitor more deeply within the active site than d/l-captopril. Unexpectedly, MMTZ binding features a thioether-pi interaction with a conserved active-site aromatic residue, consistent with their equipotent inhibition and similar binding to multiple MBLs. MMTZs penetrate multiple Enterobacterales, inhibit NDM-1 in situ, and restore carbapenem potency against clinical isolates expressing B1 MBLs. Based on their inhibitory profile and lack of eukaryotic cell toxicity, MMTZs represent a promising scaffold for MBL inhibitor development. These results also suggest sulphur-pi interactions can be exploited for general ligand design in medicinal chemistry.
		+
		+	2-Mercaptomethyl-thiazolidines use conserved aromatic-S interactions to achieve broad-range inhibition of metallo-beta-lactamases.,Rossi MA, Martinez V, Hinchliffe P, Mojica MF, Castillo V, Moreno DM, Smith R, Spellberg B, Drusano GL, Banchio C, Bonomo RA, Spencer J, Vila AJ, Mahler G Chem Sci. 2021 Jan 5;12(8):2898-2908. doi: 10.1039/d0sc05172a. PMID:34164056<ref>PMID:34164056</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6zyn" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-lactamase 3D structures\|Beta-lactamase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hinchliffe P]]	+	[[Category: Hinchliffe, P]]
-	[[Category: Spencer J]]	+	[[Category: Spencer, J]]
		+	[[Category: Antibiotic resistance]]
		+	[[Category: Antimicrobial protein]]
		+	[[Category: Inhibitor]]
		+	[[Category: Lactamase]]
		+	[[Category: Zinc]]

OCA at 08:12, 20 January 2021

OCA — Wed, 20 Jan 2021 08:12:58 GMT

←Older revision		Revision as of 08:12, 20 January 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 6zyn ~~is ON HOLD until Paper Publication~~	+	==Structure of VIM-2 with 2-Mercaptomethyl-thiazolidine L-anti-1b==
-		+	<StructureSection load='6zyn' size='340' side='right'caption='[[6zyn]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZYN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZYN FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6zyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zyn OCA], [http://pdbe.org/6zyn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zyn RCSB], [http://www.ebi.ac.uk/pdbsum/6zyn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zyn ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Hinchliffe P]]
		+	[[Category: Spencer J]]

OCA at 04:59, 2 September 2020

OCA — Wed, 02 Sep 2020 04:59:31 GMT

←Older revision		Revision as of 04:59, 2 September 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6zyn is ON HOLD	+	The entry 6zyn is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6zyn" [edit=sysop:move=sysop]

OCA — Wed, 12 Aug 2020 08:15:01 GMT

Protected "6zyn" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:15, 12 August 2020

OCA: New page: '''Unreleased structure''' The entry 6zyn is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 12 Aug 2020 08:15:00 GMT

New page: '''Unreleased structure''' The entry 6zyn is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6zyn is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]