| Sign In to gain access to subscriptions and/or personal tools. |
Enzymology of lipid A palmitoylation in bacterial outer membranesDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, russell.bishop{at}utoronto.ca, Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
The enzymology of palmitate addition to lipid A can be traced to the early discovery of monosaccharide lipid A precursors, but the functional importance of lipid A palmitoylation in bacterial resistance to the host immune response has emerged only recently. Lipid A palmitoylationin enterobacteriais determined by a PhoP/PhoQ-activated gene pagP, which encodes an unusual outer membrane enzyme of lipid A biosynthesis. PagP structure and dynamics have now been elucidated by both NMR spectroscopy and X-ray crystallography. PagP is an 8-stranded antiparallel ß-barrel preceded by an N-terminal amphipathic
Key Words: Lipid A palmitoylation • enzymology • PagP
Journal of Endotoxin Research, Vol. 10, No. 2,
107-112 (2004) |
|||
 |
|
|
 |
|
Sign In to gain access to subscriptions and/or personal tools.
-helix. The PagP barrel axis is uniquely tilted by 30° with respect to the membrane normal. An interior hydrophobic pocket in the upper half of the molecule functions as a hydrocarbon ruler, which allows the enzyme to distinguish palmitate from other acyl chains found in phospholipids. Internalization of a phospholipid palmitoyl group within the barrel appears to occur by lateral diffusion from the outer leaflet through non-hydrogen bonded regions between ß-strands. The MsbA-dependent trafficking of lipids from the inner membrane to the outer membrane outer leaflet is necessary for lipid A palmitoylation in vivo. Efforts to determine the PagP catalytic mechanism may lead to the development of inhibitors for the treatment of infections.