View source for 8jao


==Crystal structure of B1 IMP-1 MBL in complex with 2-amino-5-phenethylthiazole-4-carboxylic acid==
<StructureSection load='8jao' size='340' side='right'caption='[[8jao]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8jao]] 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=8JAO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JAO 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]] 2.194&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5ZX:2-azanyl-5-(2-phenylethyl)-1,3-thiazole-4-carboxylic+acid'>5ZX</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=8jao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jao OCA], [https://pdbe.org/8jao PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jao RCSB], [https://www.ebi.ac.uk/pdbsum/8jao PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jao ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q79MP6_PSEAI Q79MP6_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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8jao" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Li G-B]]
[[Category: Yan Y-H]]