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Mechanism of action of nucleoside antibacterial natural product antibiotics

Abstract

This article reviews the structures and biological activities of several classes of uridine-containing nucleoside antibiotics (tunicamycins, mureidomycins/pacidamycins/sansanmycins, liposidomycins/caprazamycins, muraymycins, capuramycins) that target translocase MraY on the peptidoglycan biosynthetic pathway. In particular, recent advances in structure-function studies, and recent X-ray crystal structures of translocase MraY complexed with muraymycin D2 and tunicamycin are described. The inhibition of other phospho-nucleotide transferase enzymes related to MraY by nucleoside antibiotics and analogues is also reviewed.

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Acknowledgements

Research in the author’s laboratory was supported by an EPSRC CASE PhD studentship (to RVK) with LifeArc Ltd.

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This article is part of a Special Issue commemorating Dr Kiyoshi Isono and his important contributions to the study of nucleoside antibiotics. Dr Isono led the discovery of the liposidomycin natural products in 1985, one of the first studies in this field, which established that nucleoside antibiotics could be selective antibacterial agents.

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Bugg, T.D.H., Kerr, R.V. Mechanism of action of nucleoside antibacterial natural product antibiotics. J Antibiot 72, 865–876 (2019). https://doi.org/10.1038/s41429-019-0227-3

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