Biochemical Characterization of Glutamate Racemase-A New Candidate Drug Target against Burkholderia cenocepacia Infections.
The greatest obstacle for the treatment of cystic fibrosis patients infected with the Burkholderia species is their intrinsic antibiotic resistance. For this reason, there is a need to develop new effective compounds. Glutamate racemase, an essential enzyme for the biosynthesis of the bacterial cell...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5127577?pdf=render |
| _version_ | 1811191729699684352 |
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| author | Aygun Israyilova Silvia Buroni Federico Forneris Viola Camilla Scoffone Namiq Q Shixaliyev Giovanna Riccardi Laurent Roberto Chiarelli |
| author_facet | Aygun Israyilova Silvia Buroni Federico Forneris Viola Camilla Scoffone Namiq Q Shixaliyev Giovanna Riccardi Laurent Roberto Chiarelli |
| author_sort | Aygun Israyilova |
| collection | DOAJ |
| description | The greatest obstacle for the treatment of cystic fibrosis patients infected with the Burkholderia species is their intrinsic antibiotic resistance. For this reason, there is a need to develop new effective compounds. Glutamate racemase, an essential enzyme for the biosynthesis of the bacterial cell wall, is an excellent candidate target for the design of new antibacterial drugs. To this aim, we recombinantly produced and characterized glutamate racemase from Burkholderia cenocepacia J2315. From the screening of an in-house library of compounds, two Zn (II) and Mn (III) 1,3,5-triazapentadienate complexes were found to efficiently inhibit the glutamate racemase activity with IC50 values of 35.3 and 10.0 μM, respectively. Using multiple biochemical approaches, the metal complexes have been shown to affect the enzyme activity by binding to the enzyme-substrate complex and promoting the formation of an inhibited dimeric form of the enzyme. Our results corroborate the value of glutamate racemase as a good target for the development of novel inhibitors against Burkholderia. |
| first_indexed | 2024-04-11T23:40:44Z |
| format | Article |
| id | doaj.art-014a932e98c844d88ae149dd174b250d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T23:40:44Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-014a932e98c844d88ae149dd174b250d2022-12-22T03:56:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011111e016735010.1371/journal.pone.0167350Biochemical Characterization of Glutamate Racemase-A New Candidate Drug Target against Burkholderia cenocepacia Infections.Aygun IsrayilovaSilvia BuroniFederico FornerisViola Camilla ScoffoneNamiq Q ShixaliyevGiovanna RiccardiLaurent Roberto ChiarelliThe greatest obstacle for the treatment of cystic fibrosis patients infected with the Burkholderia species is their intrinsic antibiotic resistance. For this reason, there is a need to develop new effective compounds. Glutamate racemase, an essential enzyme for the biosynthesis of the bacterial cell wall, is an excellent candidate target for the design of new antibacterial drugs. To this aim, we recombinantly produced and characterized glutamate racemase from Burkholderia cenocepacia J2315. From the screening of an in-house library of compounds, two Zn (II) and Mn (III) 1,3,5-triazapentadienate complexes were found to efficiently inhibit the glutamate racemase activity with IC50 values of 35.3 and 10.0 μM, respectively. Using multiple biochemical approaches, the metal complexes have been shown to affect the enzyme activity by binding to the enzyme-substrate complex and promoting the formation of an inhibited dimeric form of the enzyme. Our results corroborate the value of glutamate racemase as a good target for the development of novel inhibitors against Burkholderia.http://europepmc.org/articles/PMC5127577?pdf=render |
| spellingShingle | Aygun Israyilova Silvia Buroni Federico Forneris Viola Camilla Scoffone Namiq Q Shixaliyev Giovanna Riccardi Laurent Roberto Chiarelli Biochemical Characterization of Glutamate Racemase-A New Candidate Drug Target against Burkholderia cenocepacia Infections. PLoS ONE |
| title | Biochemical Characterization of Glutamate Racemase-A New Candidate Drug Target against Burkholderia cenocepacia Infections. |
| title_full | Biochemical Characterization of Glutamate Racemase-A New Candidate Drug Target against Burkholderia cenocepacia Infections. |
| title_fullStr | Biochemical Characterization of Glutamate Racemase-A New Candidate Drug Target against Burkholderia cenocepacia Infections. |
| title_full_unstemmed | Biochemical Characterization of Glutamate Racemase-A New Candidate Drug Target against Burkholderia cenocepacia Infections. |
| title_short | Biochemical Characterization of Glutamate Racemase-A New Candidate Drug Target against Burkholderia cenocepacia Infections. |
| title_sort | biochemical characterization of glutamate racemase a new candidate drug target against burkholderia cenocepacia infections |
| url | http://europepmc.org/articles/PMC5127577?pdf=render |
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