» Articles » PMID: 23163348

Metallo-β-lactamase Structure and Function

Overview
Specialty Science
Date 2012 Nov 21
PMID 23163348
Citations 226
Authors
Affiliations
Soon will be listed here.
Abstract

β-Lactam antibiotics are the most commonly used antibacterial agents and growing resistance to these drugs is a concern. Metallo-β-lactamases are a diverse set of enzymes that catalyze the hydrolysis of a broad range of β-lactam drugs including carbapenems. This diversity is reflected in the observation that the enzyme mechanisms differ based on whether one or two zincs are bound in the active site that, in turn, is dependent on the subclass of β-lactamase. The dissemination of the genes encoding these enzymes among Gram-negative bacteria has made them an important cause of resistance. In addition, there are currently no clinically available inhibitors to block metallo-β-lactamase action. This review summarizes the numerous studies that have yielded insights into the structure, function, and mechanism of action of these enzymes.

Citing Articles

Epidemiology and Genetic Traits of Carbapenemase-Producing Enterobacterales: A Global Threat to Human Health.

Alvisi G, Curtoni A, Fonnesu R, Piazza A, Signoretto C, Piccinini G Antibiotics (Basel). 2025; 14(2).

PMID: 40001385 PMC: 11852015. DOI: 10.3390/antibiotics14020141.


Functional and structural analyses of IMP-27 metallo-β-lactamase: evolution of IMP-type enzymes to overcome Zn(II) deprivation.

Kato Y, Yamaguchi T, Nakagawa-Kamura H, Ishii Y, Shimizu-Ibuka A Microbiol Spectr. 2024; :e0039124.

PMID: 39508587 PMC: 11619291. DOI: 10.1128/spectrum.00391-24.


Navigating the Current Treatment Landscape of Metallo-β-Lactamase-Producing Gram-Negative Infections: What are the Limitations?.

Grabein B, Arhin F, Daikos G, Moore L, Balaji V, Baillon-Plot N Infect Dis Ther. 2024; 13(11):2423-2447.

PMID: 39352652 PMC: 11499561. DOI: 10.1007/s40121-024-01044-8.


Approachable Synthetic Methodologies for Second-Generation -Lactamase Inhibitors: A Review.

Fatima N, Khalid S, Rasool N, Imran M, Parveen B, Kanwal A Pharmaceuticals (Basel). 2024; 17(9).

PMID: 39338273 PMC: 11434895. DOI: 10.3390/ph17091108.


The effect of combinations of a glyphosate-based herbicide with various clinically used antibiotics on phenotypic traits of Gram-negative species from the ESKAPEE group.

Zerrouki H, Hamieh A, Hadjadj L, Rolain J, Baron S Sci Rep. 2024; 14(1):21006.

PMID: 39251613 PMC: 11383965. DOI: 10.1038/s41598-024-68968-6.


References
1.
Wilke M, Lovering A, Strynadka N . Beta-lactam antibiotic resistance: a current structural perspective. Curr Opin Microbiol. 2005; 8(5):525-33. DOI: 10.1016/j.mib.2005.08.016. View

2.
Cornaglia G, Giamarellou H, Rossolini G . Metallo-β-lactamases: a last frontier for β-lactams?. Lancet Infect Dis. 2011; 11(5):381-93. DOI: 10.1016/S1473-3099(11)70056-1. View

3.
Daiyasu H, Osaka K, Ishino Y, Toh H . Expansion of the zinc metallo-hydrolase family of the beta-lactamase fold. FEBS Lett. 2001; 503(1):1-6. DOI: 10.1016/s0014-5793(01)02686-2. View

4.
Neu H . Aztreonam activity, pharmacology, and clinical uses. Am J Med. 1990; 88(3C):2S-6S; discussion 38S-42S. DOI: 10.1016/0002-9343(90)90079-s. View

5.
Materon I, Palzkill T . Identification of residues critical for metallo-beta-lactamase function by codon randomization and selection. Protein Sci. 2001; 10(12):2556-65. PMC: 2374027. DOI: 10.1110/ps.40884. View