Kinetics and regioselectivity of peptide-to-heterocycle conversions by microcin B17 synthetase

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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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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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In vitro characterization of DNA gyrase inhibition by microcin B17 analogs with altered bisheterocyclic sites.

Microcin B17 (MccB17) is a 3.1-kDa Escherichia coli antibiotic that contains thiazole and oxazole heterocycles in a peptide backbone. MccB17 inhibits its cellular target, DNA gyrase, by trapping the enzyme in a complex that is covalently bound to double-strand cleaved DNA, in a manner similar to the well-known quinolone drugs. The identification of gyrase as the target of MccB17 provides an opp...

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ژورنال

عنوان ژورنال: Chemistry & Biology

سال: 1998

ISSN: 1074-5521

DOI: 10.1016/s1074-5521(98)90071-0