Metabolomics Analysis Identifiesd-Alanine-d-Alanine Ligase as the Primary Lethal Target ofd-Cycloserine in Mycobacteria
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منابع مشابه
Metabolomics analysis identifies d-Alanine-d-Alanine ligase as the primary lethal target of d-Cycloserine in mycobacteria.
d-Cycloserine is an effective second line antibiotic used as a last resort to treat multi (MDR)- and extensively (XDR) drug resistant strains of Mycobacterium tuberculosis . d-Cycloserine interferes with the formation of peptidoglycan biosynthesis by competitive inhibition of alanine racemase (Alr) and d-alanine-d-alanine ligase (Ddl). Although the two enzymes are known to be inhibited, the in ...
متن کاملMetabolomics Reveal d-Alanine:d-Alanine Ligase As the Target of d-Cycloserine in Mycobacterium tuberculosis
Stable isotope-mass spectrometry (MS)-based metabolomic profiling is a powerful technique for following changes in specific metabolite pool sizes and metabolic flux under various experimental conditions in a test organism or cell type. Here, we use a metabolomics approach to interrogate the mechanism of antibiotic action of d-cycloserine (DCS), a second line antibiotic used in the treatment of ...
متن کاملUse of NMR metabolomics to analyze the targets of D-cycloserine in mycobacteria: role of D-alanine racemase.
D-Cycloserine (DCS) is only used with multidrug-resistant strains of tuberculosis because of serious side effects. DCS is known to inhibit cell wall biosynthesis, but the in vivo lethal target is still unknown. We have applied NMR-based metabolomics combined with principal component analysis to monitor the in vivo effect of DCS on Mycobacterium smegmatis. Our analysis suggests DCS functions by ...
متن کاملStructure of the Mycobacterium tuberculosis D-alanine:D-alanine ligase, a target of the antituberculosis drug D-cycloserine.
D-alanine:D-alanine ligase (EC 6.3.2.4; Ddl) catalyzes the ATP-driven ligation of two D-alanine (D-Ala) molecules to form the D-alanyl:D-alanine dipeptide. This molecule is a key building block in peptidoglycan biosynthesis, making Ddl an attractive target for drug development. D-Cycloserine (DCS), an analog of D-Ala and a prototype Ddl inhibitor, has shown promise for the treatment of tubercul...
متن کاملCorrection to Reinterpreting the Mechanism of Inhibition of Mycobacterium tuberculosisd-Alanine:d-Alanine Ligase by d-Cycloserine
d-Cycloserine is a second-line drug approved for use in the treatment of patients infected with Mycobacterium tuberculosis, the etiologic agent of tuberculosis. The unique mechanism of action of d-cycloserine, compared with those of other clinically employed antimycobacterial agents, represents an untapped and exploitable resource for future rational drug design programs. Here, we show that d-c...
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ژورنال
عنوان ژورنال: Journal of Proteome Research
سال: 2013
ISSN: 1535-3893,1535-3907
DOI: 10.1021/pr4010579