4K7T

Structure of the ternary complex of bacitracin, zinc, and geranyl-pyrophosphate

Summary for 4K7T

• Entry DOI: 10.2210/pdb4k7t/pdb
• Related PRD ID: PRD_001070
• Descriptor: bacitracin A2, GERANYL DIPHOSPHATE, ZINC ION, ... (5 entities in total)
• Functional Keywords: antibiotic, bacitracin, cell-wall biosynthesis inhibitor, undecaprenyl-pyrophosphate
• Biological source: Bacillus subtilis
• Total number of polymer chains: 1
• Total formula weight: 1863.35

Authors

Economou, N.J.,Loll, P.J. (deposition date: 2013-04-17, release date: 2013-08-14, Last modification date: 2024-10-16)

Primary citation

Economou, N.J.,Cocklin, S.,Loll, P.J.
High-resolution crystal structure reveals molecular details of target recognition by bacitracin.
Proc.Natl.Acad.Sci.USA, 110:14207-14212, 2013

PubMed Abstract: 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.

PubMed: 23940351
DOI: 10.1073/pnas.1308268110

Experimental method

X-RAY DIFFRACTION (1.1 Å)