Metallo-β-lactamase inhibitors inspired on snapshots from the catalytic mechanism

β-Lactam antibiotics are the most widely prescribed antibacterial drugs due to their low toxicity and broad spectrum. Their action is counteracted by different resistance mechanisms developed by bacteria. Among them, the most common strategy is the expression of β-lactamases, enzymes that hydroly...

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Detalles Bibliográficos
Autores principales: Palacios, Antonela R., Rossi, María Agustina, Mahler, Graciela S., Vila, Alejandro J.
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: MDPI 2021
Materias:
Metallo-beta-lactamases
Mechanism-based Inhibitors
Drug Resistance, Microbial
Reaction Mechanism
Acceso en línea:http://hdl.handle.net/2133/20476
http://hdl.handle.net/2133/20476
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-20476
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Metallo-beta-lactamases
Mechanism-based Inhibitors
Drug Resistance, Microbial
Reaction Mechanism
spellingShingle Metallo-beta-lactamases
Mechanism-based Inhibitors
Drug Resistance, Microbial
Reaction Mechanism
Palacios, Antonela R.
Rossi, María Agustina
Mahler, Graciela S.
Vila, Alejandro J.
Metallo-β-lactamase inhibitors inspired on snapshots from the catalytic mechanism
topic_facet Metallo-beta-lactamases
Mechanism-based Inhibitors
Drug Resistance, Microbial
Reaction Mechanism
description β-Lactam antibiotics are the most widely prescribed antibacterial drugs due to their low toxicity and broad spectrum. Their action is counteracted by different resistance mechanisms developed by bacteria. Among them, the most common strategy is the expression of β-lactamases, enzymes that hydrolyze the amide bond present in all β-lactam compounds. There are several inhibitors against serine-β-lactamases (SBLs). Metallo-β-lactamases (MBLs) are Zn(II)-dependent enzymes able to hydrolyze most β-lactam antibiotics, and no clinically useful inhibitors against them have yet been approved. Despite their large structural diversity, MBLs have a common catalytic mechanism with similar reaction species. Here, we describe a number of MBL inhibitors that mimic different species formed during the hydrolysis process: substrate, transition state, intermediate, or product. Recent advances in the development of boron-based and thiol-based inhibitors are discussed in the light of the mechanism of MBLs. We also discuss the use of chelators as a possible strategy, since Zn(II) ions are essential for substrate binding and catalysis.
format article
artículo
publishedVersion
author Palacios, Antonela R.
Rossi, María Agustina
Mahler, Graciela S.
Vila, Alejandro J.
author_facet Palacios, Antonela R.
Rossi, María Agustina
Mahler, Graciela S.
Vila, Alejandro J.
author_sort Palacios, Antonela R.
title Metallo-β-lactamase inhibitors inspired on snapshots from the catalytic mechanism
title_short Metallo-β-lactamase inhibitors inspired on snapshots from the catalytic mechanism
title_full Metallo-β-lactamase inhibitors inspired on snapshots from the catalytic mechanism
title_fullStr Metallo-β-lactamase inhibitors inspired on snapshots from the catalytic mechanism
title_full_unstemmed Metallo-β-lactamase inhibitors inspired on snapshots from the catalytic mechanism
title_sort metallo-β-lactamase inhibitors inspired on snapshots from the catalytic mechanism
publisher MDPI
publishDate 2021
url http://hdl.handle.net/2133/20476
http://hdl.handle.net/2133/20476
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AT rossimariaagustina metalloblactamaseinhibitorsinspiredonsnapshotsfromthecatalyticmechanism
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bdutipo_str Repositorios
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