4K7T | pdb_00004k7t

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

(2013) Proc Natl Acad Sci U S A 110: 14207-14212

• PubMed: 23940351 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1073/pnas.1308268110
• Primary Citation of Related Structures:  
  4K7T


• 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.

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Organizational Affiliation: 

Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.