Glutamate Racemase As a Target for Drug Discovery

Overview

Journal Microb Biotechnol

Specialties Biotechnology
Microbiology

Date 2011 Jan 26

PMID 21261855

Citations 33

Authors

Stewart L Fisher

Affiliations

Soon will be listed here.

Abstract

The bacterial cell wall is a highly cross-linked polymeric structure consisting of repeating peptidoglycan units, each of which contains a novel pentapeptide substitution which is cross-linked through transpeptidation. The incorporation of D-glutamate as the second residue is strictly conserved across the bacterial kingdom. Glutamate racemase, a member of the cofactor-independent, two-thiol-based family of amino acid racemases, has been implicated in the production and maintenance of sufficient d-glutamate pool levels required for growth. The subject of over four decades of research, it is now evident that the enzyme is conserved and essential for growth across the bacterial kingdom and has a conserved overall topology and active site architecture; however, several different mechanisms of regulation have been observed. These traits have recently been targeted in the discovery of both narrow and broad spectrum inhibitors. This review outlines the biological history of this enzyme, the recent biochemical and structural characterization of isozymes from a wide range of species and developments in the identification of inhibitors that target the enzyme as possible therapeutic agents.

Citing Articles

Identification and prioritization of novel therapeutic candidates against glutamate racemase from Klebsiella pneumoniae.

Kumar A, Anjum F, Hassan M, Shamsi A, Singh R PLoS One. 2025; 20(2):e0317622.

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Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates.

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Screening and Identification of Natural Compounds as Potential Inhibitors of Glutamate Racemase, an Emerging Drug Target of Food Pathogen O157:H7: An Approach to Combat Increasing Drug Resistance.

Kumar R, Gupta S, Adhana S, Khanna A, Sahoo S, Faiza M Infect Disord Drug Targets. 2024; 25(2):e18715265306131.

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A prototrophic suppressor of a D-glutamate auxotroph reveals a member of the periplasmic broad-spectrum racemase family (BsrF).

Coppinger M, Laramore K, Popham D, Stabb E J Bacteriol. 2024; 206(3):e0033323.

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