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Showing 1 to 20 of 20 for “"mycothiol"”.
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Synthesis of analogues of mycothiol as possible inhibitors of enzymes in the biosynthesis of mycothiol
Mycobacterium tuberculosis is the causative agent of tuberculosis and is a leading pathogenic cause of death worldwide. The rise of mycobacterial resistance to common antituberculars such as isoniazid and rifampicin, along with the lethal alliance of HIV and M. tuberculosis co-infection, has led to …
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Mycothiol disulfide reductase as a drug target
Includes abstract. Includes bibliographical references (leaves 154-171).
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Helical reconstruction of Mycobacterium smegmatis Mycothiol S-conjugate amidase filaments
The metabolic pathway of mycothiol (MSH) is a major cellular defence against oxidative stress, and several antibiotics for mycobacteria, including Mycobacterium tuberculosis. The central enzyme used in the clearance of electrophilic toxins is Mycothiol S-conjugate amidase (Mca). Mca is similar to a …
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Inhibition of a Mycothiol biosynthetic enzyme and a detoxification enzyme as anti-tubercular drug targets
Includes abstract. Includes bibliographical references (leaves 131-141).
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Design and synthesis of potential inhibitors of enzymes involved in the biosynthesis and utilisation of mycothiol
… carbazole-1,4-quinone-derived conjugates of a mycothiol-like scaffold designed to act as redox cycling subversive substrates of the enzyme, Mtr, or potentially inhibit other mycothiol-dependent or biosynthetic enzymes, in order to develop novel antitubercular lead compounds. The expression and …
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Substrate binding to MshB, a zinc-dependent deacetylase in the mycothiol biosynthetic pathway of Mycobacterium tuberculosis
… In mycobacteria a carbohydrate-based thiol, mycothiol (MSH), is used instead. MshB catalyses the third step in the mycothiol biosynthetic pathway which involves the deacetylation of 1-O-(2-acetamido-2-deoxy-α-D-glucopyranosyl)-D-myo-inositol (GlcNAcIns), via cleavage of an amide bond, to …
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New synthetic routes to functionalized 2-C-alkylglucosides, precursors of potential inhibitors of mycothiol biosynthesis in the Mycobacteria
… a N-deacetylase involved in the biosynthesis of mycothiol in the Mycobacteria, including M. tuberculosis, the causative agent of TB. Mycothiol is a low molecular weight thiol produced by Mycobacteria as a defense against oxidative stress and xenobiotics, and the enzymes involved in its …
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Synthesis of side-chain-modified mycothiol analogues incorporating carbazole quinones, and evaluation as inhibitors of enzymes in the Mycobacteria
Mycothiol is found only in Actinobacteria including M. tuberculosis, and appears to play an important role in the bacterium's defence against xenobiotics and oxidative stress. The biosynthetic pathway to this pseudo-disaccharide has been elucidated and a range of mycothiol-dependent enzymes have …
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Rationalising the inhibition of M. tuberculosis MshB by a series of inhibitors constructed from plumbagin conjugated via a viariable alkyl linker to a phenyl thioglycoside
… 1.7 million TB related deaths worldwide. Mycothiol is produced in M. tuberculosis as the dominant low molecular weight thiol and is thought to protect the bacteria against oxidative stress. Since mycothiol is unique to Actinomycetes and is also proposed to play an important role in the …
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Identification of native co-factors of MshB and MCA from Mycobacterium species
Mycothiol (MSH), a low-molecular- weight thiol, is a primary reducing agent and essential for the survival of mycobacteria. The full pathway of MSH biosynthesis and detoxification includes various promising drug targets. Several metalloenzymes are involved in this pathway, such as a deacetylase …
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Conditions affecting ergothioneine levels in Mycobacterium smegmatis & the attempted isolation of α-N, N, N-Histidine methyltransferase, the first enzyme in ergothioneine biosynthesis
Ergothioneine and mycothiol are the two major low molecular weight thiols present in mycobacteria. The generation of mycothiol-deficient mutants has demonstrated its role in protecting M tuberculosis against oxidative and nitrosative stress. To date, no ergothioneine-deficient mutants have been …
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Development of new methodologies for functionalizing glycals and 1,2-cyclopropanated sugars, and applications in the synthesis of inhibitors of enzymes in the Mycobacteria
… and secures its survival. Studies have shown the mycothiol-deficient bacteria are hypersensitive to external stresses and hence inhibition of the biosynthesis of mycothiol could be a drug lead against TB.
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Biosynthetic and Functional Studies of Bacillithiol in Gram-positive Bacteria
… cells as well as Gram-negative bacteria and mycothiol (MSH) as the dominant LMW thiol in Actinobacteria. Functional studies on those thiols have revealed their importance in cell metabolism, also their potential as target for antimicrobial development. Interestingly, neither GSH nor MSH was …
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Elucidation of mechanisms of antibiotic subversion in mycobacteria
… effects, ex vivo, when compared to VER. Mycothiol-mediated protection : It was hypothesized that undetectable levels of mycothiol ( MSH ) in Mtb would potentiate the use of current antibiotics. To investigate the contribution of the cellular antioxidant, MSH, to the mitigation of …
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Synthesis and evaluation of M.tb Glycosyltransferase (MshA) inhibitors
… and substrate mimics, aimed at targeting the mycothiol biosynthetic pathway which is specific to mycobacteria. The strategy involved design of molecules that are expected to compete for the UDP-GlcNAc binding site of the glycosyltransferase (MshA) of M.tb. The bioactivity of the designed …
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Synthesis of Mycobacterial Ergothioneine biosynthetic pathway metabolites
… protective molecule, glutathione and produce mycothiol (MSH) and ergothioneine (ESH) as their principal low molecular mass thiol instead. Ergothioneine has been known for a while as an anti-oxidant; however its role as a protective thiol in Mycobacterium tuberculosis is still undefined. …
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Enzymatic Characterization of N-Acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside Deacetylase (MshB)
… (TB), produce inositol derivatives including mycothiol (MSH). MSH is a unique and dominant cytosolic thiol that protects mycobacterial pathogens against the damaging effects of reactive oxygen species and is involved in antibiotic detoxification. Therefore, MSH is considered a potential drug …
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Synthesis of thiohistidines and its metabolic pathway precursors
… such as Mycobacterium tuberculosis produce mycothiol and ergothioneine as their principal low molecular mass thiols. It is only very recently that the link between ergothioneine and tuberculosis disease has started to emerge, these studies suggested that ergothioneine is essential for the …
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Disabling the intrinsic resistome of Mycobacterium tuberculosis: elucidating hierarchies of DNA repair and mutagenesis that undermine current antibiotic efficacy
… which is involved in glycogen biosynthesis, and mycothiol biosynthesis proteins, MSMEG_0933 and MSMEG_5261, as compensating the absence of UvrB during MMC treatment. Under MOX treatment, the absence of UvrB was compensated by the RecC/Single-strand Annealing pathway. In contrast, DnaE2 deficiency …
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Application of hydrogen deuterium exchange mass spectrometry in protein-ligand and protein-protein interactions
… (CgMshA) catalyzes the initial step of mycothiol biosynthesis. A large conformational change was observed in CgMshA on nucleotide binding by superimposing APO structure of CgMshA and complex structure with UDP. HDX-MS was utilized to study conformational changes of CgMshA on substrate …