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The antibiotic microcin B17 is a DNA gyrase poison: characterisation of the mode of inhibition11Edited by J. Karn

2001; Elsevier BV; Volume: 307; Issue: 5 Linguagem: Inglês

10.1006/jmbi.2001.4562

1089-8638

Jonathan G. Heddle, Stephen J. Blance, Deborah B. Zamble, Florian Hollfelder, Deborah A. Miller, Lois M. Wentzell, Christopher T. Walsh, Anthony Maxwell,

Synthesis and bioactivity of alkaloids

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 β,γ-imidodiphosphate, microcin B17 stabilises a gyrase-dependent DNA cleavage complex in a manner reminiscent of quinolones, Ca2+, or the bacterial toxin CcdB. The pattern of DNA cleavage produced by gyrase in the presence of microcin B17 is different from that produced by quinolones and more closely resembles Ca2+-mediated cleavage. Several gyrase mutants, including well-known quinolone-resistant mutants, are cross resistant to microcin-induced DNA cleavage. We suggest that microcin exerts its effects through a mechanism that has similarities to those of both the bacterial toxin CcdB and the quinolone antibacterial agents.