Mechanism of action of nucleoside antibacterial natural product antibiotics

Timothy D H Bugg; Rachel V Kerr

doi:10.1038/s41429-019-0227-3

Mechanism of action of nucleoside antibacterial natural product antibiotics

J Antibiot (Tokyo). 2019 Dec;72(12):865-876. doi: 10.1038/s41429-019-0227-3. Epub 2019 Aug 30.

Authors

Timothy D H Bugg¹, Rachel V Kerr²

Affiliations

¹ Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK. T.D.Bugg@warwick.ac.uk.
² Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.

PMID: 31471595
DOI: 10.1038/s41429-019-0227-3

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology*
Bacterial Proteins / antagonists & inhibitors
Bacterial Proteins / metabolism
Biological Products / chemistry*
Biological Products / pharmacology*
Nucleosides / chemistry
Nucleosides / pharmacology*
Peptidoglycan / metabolism
Transferases (Other Substituted Phosphate Groups)
Transferases / antagonists & inhibitors
Transferases / metabolism
Uridine / analogs & derivatives
Uridine / chemistry

Substances

Anti-Bacterial Agents
Bacterial Proteins
Biological Products
Nucleosides
Peptidoglycan
Transferases
Transferases (Other Substituted Phosphate Groups)
mraY protein, Bacteria
Uridine