Crystal Structure of ADP-L-Glycero-D-mannoheptose 6-epimerase(Site not responding. Last check: 2007-10-03)
Heptose is an obligatory component of the LPS core domain; its absence results in a truncated LPS structure resulting in susceptibility to hydrophobic antibiotics.
Heptose is not found in mammalian cells, thus its biosynthetic pathway in bacteria presents a unique target for the design of novel antimicrobial agents.
The structure of AGME, in complex with NADP and the catalytic inhibitor ADP-glucose, has been determined at 2.0 Å resolution by multiwavelength anomalous diffraction (MAD) phasing methods.
Our current research initiatives emphasize the understanding of the structure and function of LPS biosynthetic enzymes, the role of LPS in the pathology of E. coli and Helicobacter pylori and the evaluation of specific enzymes in the LPS biosynthesis pathway as potential novel antibiotic targets.
L-Glycero-D-mannoheptose (heptose) is a 7-carbon sugar present in the lipopolysaccharide of a wide variety of gram-negative bacteria.
Heptose provides a link between lipid A-KDO, the outer core and the O-antigen regions of LPS.
[Structure of the heptose region of the lipopolysaccharide from Escherichia coli K12 CR34 (author's transl)] -- Blache ...(Site not responding. Last check: 2007-10-03)
[Structure of the heptose region of the lipopolysaccharide from Escherichia coli K12 CR34 (author's transl)] -- Blache et al.
The heptose region of the lipopolysaccharide of Escherichia coli K12 CR34
sugars of the linear chain, heptose I, heptose II and glucose are
LOS and appears to be involved in heptose biosynthesis.
for heptose incorporation, it is distinct from the kinase and
Sirisena, D. M., MacLachlan, P. R., Liu, S.-l., Hessel, A. and Sanderson, K. Molecular analysis of the rfaD gene, for heptose synthesis, and the rfaF gene, for heptose transfer, in lipopolysaccharide synthesis in Salmonella typhimurium.
rfaF -(Site not responding. Last check: 2007-10-03)
The rfaD gene encodes a polypeptide of 35 kDa and the rfaF encodes a protein of 39 kDa, as demonstrated by in vitro transcription-translation studies.
Molecular analysis of the rfaD gene, for heptose synthesis, and the rfaF gene, for heptose transfer, in lipopolysaccharide synthesis in Salmonella typhimurium.
ColB2 transfer was more strongly affected by mutations in the heptose II-heptose III region of the LPS (rfaF) whereas R100-1 was not strongly affected by any of the rfa mutations tested.
The reaction catalyzed by LgtK is shown with the acceptor LPS shown as the inner core intermediate, which has the terminal heptose acceptor for LgtK.
Garegg, P.J., Oscarson, S., Ritzen, H., and Szonyi, M. (1992) Synthesis of 2-(4-trifluoroacetamidophenyl)ethyl O-(L-glycero-alpha-D-manno- hepto pyranosyl)-(1-7)-O-(L-glycero-alpha-D-manno- heptopyranosyl)-(1-3)- L-glycero-alpha-D-manno-heptopyranoside, corresponding to the heptose region of the Salmonella ra core structure.
