This family consists of several bacterial antimicrobial peptide resistance and lipid A acylation (PagP) proteins. In a number of pathogenic Gram-negative bacteria, PagP offers resistance to certain cationic antimicrobial peptides produced during the host innate immune response. PagP is an integral outer membrane enzyme (acyltransferase) that transfers a palmitate chain from a phospholipid to lipid A (endotoxin). PagP is indispensable for lipid A palmitoylation in Gram-negative bacteria and has been implicated in resistance to host immune defenses. PagP possesses an unusual structure for an integral membrane protein, with a highly dynamic barrel domain that is tilted with respect to the membrane normal. PagP can distinguish lipid acyl chains that differ by a single methylene unit, indicating that the enzyme possesses a remarkably precise hydrocarbon ruler. The crystal structure of PagP from Escherichia coli has been solved, suggesting an 8-stranded ß-barrel, preceded by an amphipathic alpha helix, with an interior hydrophobic pocket occupied by a single detergent molecule. Acyl-group specificity is modulated by mutation of Gly(88) lining the bottom of the hydrophobic pocket and therefore confirming the hydrocarbon ruler mechanism for palmitate recognition. Three amino acid residues, critical for enzymatic activity are localized to extracellular loops in order to interact with the polar head groups of lipid A. Hence, the active site of PagP is situated on the outer surface of the outer membrane, similar to the outer membrane phospholipases.

Representative image: