Logo image
Back
High-resolution crystal structure reveals molecular details of target recognition by bacitracin
Journal article   Open access

High-resolution crystal structure reveals molecular details of target recognition by bacitracin

Nicoleta J Economou, Simon Cocklin and Patrick J Loll
Proceedings of the National Academy of Sciences - PNAS, v 110(35), pp 14207-14212
27 Aug 2013
DOI: https://doi.org/10.1073/pnas.1308268110
PMID: 23940351
url
https://doi.org/10.1073/pnas.1308268110View
Published, Version of Record (VoR) Open

Abstract

Surface Plasmon Resonance Amino Acid Sequence Models, Molecular Molecular Sequence Data Protein Binding Crystallography, X-Ray Protein Conformation Cell Membrane - metabolism Polyisoprenyl Phosphates - metabolism Bacitracin - chemistry Bacitracin - metabolism
Bacitracin is a metalloantibiotic agent that is widely used as a medicine and feed additive. It interferes with bacterial cell-wall biosynthesis by binding undecaprenyl-pyrophosphate, a lipid carrier that serves as a critical intermediate in cell wall production. Despite bacitracin's broad use, the molecular details of its target recognition have not been elucidated. Here we report a crystal structure for the ternary complex of bacitracin A, zinc, and a geranyl-pyrophosphate ligand at a resolution of 1.1 Å. The antibiotic forms a compact structure that completely envelopes the ligand's pyrophosphate group, together with flanking zinc and sodium ions. The complex adopts a highly amphipathic conformation that offers clues to antibiotic function in the context of bacterial membranes. Bacitracin's efficient sequestration of its target represents a previously unseen mode for the recognition of lipid pyrophosphates, and suggests new directions for the design of next-generation antimicrobial agents.

Metrics

8 Record Views
77 citations in Web of Science
71 citations in Scopus

Details

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Biochemistry & Molecular Biology
Logo image