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Publication Abstract from PubMed

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 A. 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.

High-resolution crystal structure reveals molecular details of target recognition by bacitracin.,Economou NJ, Cocklin S, Loll PJ Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14207-12. doi:, 10.1073/pnas.1308268110. Epub 2013 Aug 12. PMID:23940351^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.