Structures of Bacterial MraY and Human GPT Provide Insights into Rational Antibiotic Design.

Journal Article (Journal Article;Review)

The widespread emergence of antibiotic resistance in pathogens necessitates the development of antibacterial agents inhibiting underexplored targets in bacterial metabolism. One such target is phospho-MurNAc-pentapeptide translocase (MraY), an essential integral membrane enzyme that catalyzes the first committed step of peptidoglycan biosynthesis. MraY has long been considered a promising candidate for antibiotic development in part because it is the target of five classes of naturally occurring nucleoside inhibitors with potent in vivo and in vitro antibacterial activity. Although these inhibitors each have a nucleoside moiety, they vary dramatically in their core structures, and they have different activity properties. Until recently, the structural basis of MraY inhibition was poorly understood. Several recent structures of MraY and its human paralog, GlcNAc-1-P-transferase, have provided insights into MraY inhibition that are consistent with known inhibitor activity data and can inform rational drug design for this important antibiotic target.

Full Text

Duke Authors

Cited Authors

  • Mashalidis, EH; Lee, S-Y

Published Date

  • August 21, 2020

Published In

Volume / Issue

  • 432 / 18

Start / End Page

  • 4946 - 4963

PubMed ID

  • 32199982

Pubmed Central ID

  • PMC8351759

Electronic International Standard Serial Number (EISSN)

  • 1089-8638

Digital Object Identifier (DOI)

  • 10.1016/j.jmb.2020.03.017

Language

  • eng

Conference Location

  • England