OCA at 13:09, 1 November 2023

OCA — Wed, 01 Nov 2023 13:09:04 GMT

←Older revision		Revision as of 13:09, 1 November 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8hyd is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of B1 VIM-2 MBL in complex with 2-amino-5-(2-(thiophen-2-yl)ethyl)thiazole-4-carboxylic acid==
		+	<StructureSection load='8hyd' size='340' side='right'caption='[[8hyd]], [[Resolution\|resolution]] 1.71Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8hyd]] 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=8HYD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HYD FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.71Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=60J:2-azanyl-5-(2-thiophen-2-ylethyl)-1,3-thiazole-4-carboxylic+acid'>60J</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=8hyd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hyd OCA], [https://pdbe.org/8hyd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hyd RCSB], [https://www.ebi.ac.uk/pdbsum/8hyd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hyd ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q9K2N0_PSEAI Q9K2N0_PSEAI]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Metallo-beta-lactamases (MBLs) are zinc-dependent enzymes capable of hydrolyzing all bicyclic beta-lactam antibiotics, posing a great threat to public health. However, there are currently no clinically approved MBL inhibitors. Despite variations in their active sites, MBLs share a common catalytic mechanism with carbapenems, forming similar reaction species and hydrolysates. We here report the development of 2-aminothiazole-4-carboxylic acids (AtCs) as broad-spectrum MBL inhibitors by mimicking the anchor pharmacophore features of carbapenem hydrolysate binding. Several AtCs manifested potent activity against B1, B2, and B3 MBLs. Crystallographic analyses revealed a common binding mode of AtCs with B1, B2, and B3 MBLs, resembling binding observed in the MBL-carbapenem product complexes. AtCs restored Meropenem activity against MBL-producing isolates. In the murine sepsis model, AtCs exhibited favorable synergistic efficacy with Meropenem, along with acceptable pharmacokinetics and safety profiles. This work offers promising lead compounds and a structural basis for the development of potential drug candidates to combat MBL-mediated antimicrobial resistance.

-	~~Authors: Yan, Y.~~-H., ~~Zhu~~, ~~K.-~~R., Li, G.-B.	+	Discovery of 2-Aminothiazole-4-carboxylic Acids as Broad-Spectrum Metallo-beta-lactamase Inhibitors by Mimicking Carbapenem Hydrolysate Binding.,Yan YH, Zhang TT, Li R, Wang SY, Wei LL, Wang XY, Zhu KR, Li SR, Liang GQ, Yang ZB, Yang LL, Qin S, Li GB J Med Chem. 2023 Oct 12;66(19):13746-13767. doi: 10.1021/acs.jmedchem.3c01189. , Epub 2023 Oct 4. PMID:37791640<ref>PMID:37791640</ref>

-	~~Description: Crystal structure~~ of ~~B1 VIM-2 MBL in complex with 2-amino-5~~-(2-~~(thiophen-2-yl)ethyl)thiazole-4-carboxylic acid~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Li, G.-B]]	+	<div class="pdbe-citations 8hyd" style="background-color:#fffaf0;"></div>
-	[[Category: Yan, Y.-H]]	+	== References ==
-	[[Category: Zhu, K.-R]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Pseudomonas aeruginosa]]
		+	[[Category: Li G-B]]
		+	[[Category: Yan Y-H]]
		+	[[Category: Zhu K-R]]

OCA at 05:22, 18 January 2023

OCA — Wed, 18 Jan 2023 05:22:24 GMT

←Older revision		Revision as of 05:22, 18 January 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8hyd is ON HOLD	+	The entry 8hyd is ON HOLD until Paper Publication

	Authors: Yan, Y.-H., Zhu, K.-R., Li, G.-B.		Authors: Yan, Y.-H., Zhu, K.-R., Li, G.-B.

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

OCA — Wed, 11 Jan 2023 06:21:35 GMT

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

←Older revision

Revision as of 06:21, 11 January 2023

OCA: New page: '''Unreleased structure''' The entry 8hyd is ON HOLD Authors: Yan, Y.-H., Zhu, K.-R., Li, G.-B. Description: Crystal structure of B1 VIM-2 MBL in complex with 2-amino-5-(2-(thiophen-2-...

OCA — Wed, 11 Jan 2023 06:21:34 GMT

New page: '''Unreleased structure''' The entry 8hyd is ON HOLD Authors: Yan, Y.-H., Zhu, K.-R., Li, G.-B. Description: Crystal structure of B1 VIM-2 MBL in complex with 2-amino-5-(2-(thiophen-2-...

New page

'''Unreleased structure'''

The entry 8hyd is ON HOLD

Authors: Yan, Y.-H., Zhu, K.-R., Li, G.-B.

Description: Crystal structure of B1 VIM-2 MBL in complex with 2-amino-5-(2-(thiophen-2-yl)ethyl)thiazole-4-carboxylic acid
[[Category: Unreleased Structures]]
[[Category: Li, G.-B]]
[[Category: Yan, Y.-H]]
[[Category: Zhu, K.-R]]

8hyd - Revision history

OCA at 13:09, 1 November 2023

OCA at 05:22, 18 January 2023

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

OCA: New page: '''Unreleased structure''' The entry 8hyd is ON HOLD Authors: Yan, Y.-H., Zhu, K.-R., Li, G.-B. Description: Crystal structure of B1 VIM-2 MBL in complex with 2-amino-5-(2-(thiophen-2-...