I know little of chemistry and expect to be dead wrong, but this caught my eye. First of all, there is the involvement of my pet gram-negative bacteria's toxins. Second, there is the necessity for iron's involvement. Does it lead anywhere?


1: Biochemistry. 2008 Mar 4;47(9):2814-25. Epub 2008 Feb 7.

An inner membrane dioxygenase that generates the 2-hydroxymyristate moiety of
Salmonella lipid A.

Gibbons HS, Reynolds CM, Guan Z, Raetz CR.

Department of Biochemistry, Duke University Medical Center, Durham, North
Carolina 27710, USA.

The lipid A residues of certain Gram-negative bacteria, including most strains of
Salmonella and Pseudomonas, are esterified with one or two secondary
S-2-hydroxyacyl chains. The S-2 hydroxylation process is O 2-dependent in vivo,
but the relevant enzymatic pathways have not been fully characterized because in
vitro assays have not been developed. We previously reported that expression of
the Salmonella lpxO gene confers upon Escherichia coli K-12 the ability to
synthesize 2-hydroxymyristate modified lipid A ( J. Biol. Chem. (2000) 275,
32940-32949). We now demonstrate that inactivation of lpxO, which encodes a
putative Fe (2+)/O 2/alpha-ketoglutarate-dependent dioxygenase, abolishes
S-2-hydroxymyristate formation in S. typhimurium. Membranes of E. coli strains
expressing lpxO are able to hydroxylate Kdo 2-[4'- (32)P]-lipid A in vitro in the
presence of Fe (2+), O 2, alpha-ketoglutarate, ascorbate, and Triton X-100. The
Fe (2+) chelator 2,2'-bipyridyl inhibits the reaction. The product generated in
vitro is a monohydroxylated Kdo 2-lipid A derivative. The [4'- (32)P]-lipid A
released by mild acid hydrolysis from the in vitro product migrates with
authentic S-2-hydroxlyated lipid A isolated from (32)P-labeled S. typhimurium
cells. Electrospray ionization mass spectrometry and gas chromatography/mass
spectrometry of the in vitro product are consistent with the 2-hydroxylation of
the 3'-secondary myristoyl chain of Kdo 2-lipid A. LpxO contains two predicted
trans-membrane helices (one at each end of the protein), and its active site
likely faces the cytoplasm. LpxO is an unusual example of an integral membrane
protein that is a member of the Fe (2+)/O 2/alpha-ketoglutarate-dependent
dioxygenase family.


PMID: 18254598 [PubMed - indexed for MEDLINE]