Expressed protein ligation to probe regiospecificity of heterocyclization in the peptide antibiotic microcin B17

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Expressed protein ligation to probe regiospecificity of heterocyclization in the peptide antibiotic microcin B17.

BACKGROUND The Escherichia coli peptide antibiotic microcin B17 (MccB17) contains thiazole and oxazole heterocycles derived from a distributive yet directional cyclization of cysteines and serines in the McbA precursor catalyzed by MccB17 synthetase. Whether the formation of upstream rings potentiates downstream heterocyclization has not been previously determined. RESULTS McbA fragments (46-...

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Posttranslational heterocyclization of cysteine and serine residues in the antibiotic microcin B17: distributivity and directionality.

To produce the antibiotic Microcin B17, four Cys and four Ser residues are converted into four thiazoles and four oxazoles by the three subunit Microcin B17 synthetase. High-resolution mass spectrometry (MS) was used to monitor the kinetics of posttranslational heterocyclic ring formation (-20 Da per ring) and demonstrated the accumulation of all intermediates, from one to seven rings, indicati...

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The antibiotic microcin B17 is a DNA gyrase poison: characterisation of the mode of inhibition.

Microcin B17 is a 3.1-kDa bactericidal peptide; the putative target of this antibiotic is DNA gyrase. Microcin B17 has no detectable effect on gyrase-catalysed DNA supercoiling or relaxation activities in vitro and is unable to stabilise DNA cleavage in the absence of nucleotides. However, in the presence of ATP, or the non-hydrolysable analogue 5'-adenylyl beta,gamma-imidodiphosphate, microcin...

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Computational design of the lasso peptide antibiotic microcin J25.

Microcin J25 (MccJ25) is a 21 amino acid (aa) ribosomally synthesized antimicrobial peptide with an unusual structure in which the eight N-terminal residues form a covalently cyclized macrolactam ring through which the remaining 13 aa tail is fed. An open question is the extent of sequence space that can occupy such an extraordinary, highly constrained peptide fold. To begin answering this ques...

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Fragments of the Bacterial Toxin Microcin B17 as Gyrase Poisons

Fluoroquinolones are very important drugs in the clinical antibacterial arsenal; their success is principally due to their mode of action: the stabilisation of a gyrase-DNA intermediate (the cleavage complex), which triggers a chain of events leading to cell death. Microcin B17 (MccB17) is a modified peptide bacterial toxin that acts by a similar mode of action, but is unfortunately unsuitable ...

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ژورنال

عنوان ژورنال: Chemistry & Biology

سال: 1999

ISSN: 1074-5521

DOI: 10.1016/s1074-5521(99)80126-4