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Glutamate racemase as a target for drug discovery
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 acro...
Autor principal: | |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815242/ https://www.ncbi.nlm.nih.gov/pubmed/21261855 http://dx.doi.org/10.1111/j.1751-7915.2008.00031.x |
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author | Fisher, Stewart L. |
author_facet | Fisher, Stewart L. |
author_sort | Fisher, Stewart L. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3815242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-38152422014-02-12 Glutamate racemase as a target for drug discovery Fisher, Stewart L. Microb Biotechnol Reviews 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. Blackwell Publishing Ltd 2008-09 2008-08-18 /pmc/articles/PMC3815242/ /pubmed/21261855 http://dx.doi.org/10.1111/j.1751-7915.2008.00031.x Text en Copyright © 2008 The Author. Journal compilation © 2008 Society for Applied Microbiology and Blackwell Publishing Ltd |
spellingShingle | Reviews Fisher, Stewart L. Glutamate racemase as a target for drug discovery |
title | Glutamate racemase as a target for drug discovery |
title_full | Glutamate racemase as a target for drug discovery |
title_fullStr | Glutamate racemase as a target for drug discovery |
title_full_unstemmed | Glutamate racemase as a target for drug discovery |
title_short | Glutamate racemase as a target for drug discovery |
title_sort | glutamate racemase as a target for drug discovery |
topic | Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815242/ https://www.ncbi.nlm.nih.gov/pubmed/21261855 http://dx.doi.org/10.1111/j.1751-7915.2008.00031.x |
work_keys_str_mv | AT fisherstewartl glutamateracemaseasatargetfordrugdiscovery |