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Transfer of palmitate from phospholipids to lipid A in outer membranes of Gram‐negative bacteria
Author(s) -
Bishop Russell E.,
Gibbons Henry S.,
Guina Tina,
Trent M. Stephen,
Miller Samuel I.,
Raetz Christian R. H.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.19.5071
Subject(s) - biology , bacteria , membrane , gram negative bacteria , gram , biochemistry , gram positive bacteria , bacterial outer membrane , microbiology and biotechnology , escherichia coli , genetics , gene
Regulated covalent modifications of lipid A are implicated in virulence of pathogenic Gram‐negative bacteria. The Salmonella typhimurium PhoP/PhoQ‐activated gene pagP is required both for biosynthesis of hepta‐acylated lipid A species containing palmitate and for resistance to cationic anti‐microbial peptides. Palmitoylated lipid A can also function as an endotoxin antagonist. We now show that pagP and its Escherichia coli homolog ( crcA ) encode an unusual enzyme of lipid A biosynthesis localized in the outer membrane. PagP transfers a palmitate residue from the sn ‐1 position of a phospholipid to the N‐linked hydroxymyristate on the proximal unit of lipid A (or its precursors). PagP bearing a C‐terminal His 6 ‐tag accumulated in outer membranes during overproduction, was purified with full activity and was shown by cross‐linking to behave as a homodimer. PagP is the first example of an outer membrane enzyme involved in lipid A biosynthesis. Additional pagP homologs are encoded in the genomes of Yersinia and Bordetella species. PagP may provide an adaptive response toward both Mg 2+ limitation and host innate immune defenses.