CSDB: Search results

References to other databases: GTC:G19436DI, GlycomeDB:28027
Structural formula & atomic coordinates
Sweet-II 3D model
Show glycosyltransferases

Lipopolysaccharides (LPS) are the endotoxins of Gram-negative bacteria and very well known for their immunological, pharmacological and pathophysiological effects displayed in eucaryotic cells and organisms. To date, much emphasis has been put on the elucidation of the chemical structures of LPS and on their relation, or that of substructures, to the various biological effects. The lipid part of LPS, the lipid A, was proven to represent the toxic principle of endotoxin. However, lipid A toxicity depends strongly on its structure, and is influenced by a second region of LPS, the core region, that is covalently linked to lipid A. Also, the core region possesses immunogenic properties. Therefore, complete structural analyses of the core region and the comparison of its structures with biological features of LPS are of high importance for a better understanding of LPS action, and one prerequesite for strategies aimed at the treatment of endotoxicosis. In the past, quite a number of structures of the core regions from various Gram-negative bacteria were published and summarized in several overviews. The present review adds to this knowledge those structures that were published between October 1998 and December 2001.

lipopolysaccharides, heptose, Kdo, chemical structure, core region, tructure

Publication DOI: 10.4052/tigg.14.87
Journal NLM ID: 9425898
Correspondence: oholst@fz-borstel.de
Institutions: Structural Biochemistry, Research Center Borstel, Center for Medicine and Biosciences, Borstel, Germany

Early steps in the biosynthesis of lipopolysaccharide (LPS) involve the transfer of 3-deoxy-α-D-manno-oct-2-ulopyranosonic acid (Kdo) to lipid A. Whereas Kdo transferases (WaaA) of Escherichia coli generate a (2→4)-linked Kdo disaccharide, Chlamydiae contain tri- or tetra-functional WaaA generating oligosaccharides with (2→8)- and (2→4)-linkages between Kdo. It has been suggested that the transfer of L-glycero-α-D-manno-heptose (Hep) to Kdo by an E. coli WaaC may not be possible in the presence of (2→8)-linked Kdo. E. coli double-mutants deficient in heptosyltransferases I (waaC) and II (waaF) and expressing waaA of Chlamydiae instead of their own, make Chlamydia-type Kdo oligosaccharides which are attached to an E. coli lipid A. Using such strains expressing waaA of Chlamydophila pneumoniae, Chlamydophila psittaci, or Chlamydia trachomatis, we have studied the effect of E. coli waaC gene expression on LPS structure. Structural analyses revealed the formation of two novel oligosaccharides Hep-(1→5)[Kdo-(2→4)]-Kdo and Hep-(1→5)[Kdo-(2→8)-Kdo-(2→4)]-Kdo showing that Hep is transferred in the presence of (2→8)-linked Kdo. Surprisingly, the transfer of Hep onto Kdo-(2→4)-Kdo-(2→4)-Kdo did not occur, despite the fact that Hep-(1→5)[Kdo-(2→4)-Kdo-(2→4)]-Kdo is found in nature as a partial structure of E. coli LPS. The premature end of the biosynthesis and incorporation of Hep into the LPS indicated that WaaC had access to the substrate before Kdo transfer was completed. We have observed differences between WaaA of C. trachomatis, C. pneumoniae and C. psittaci which indicate mechanistic differences between these Kdo transferases

biosynthesis, LPS, Escherichia coli, Kdo, Hep, WaaA, WaaC, WaaF, Chlamydiae

NCBI PubMed ID: 19201821
Journal NLM ID: 101469670
Publisher: Sage Publications
Correspondence: sml@fz-borstel.de
Institutions: Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany
Methods: 13C NMR, 1H NMR, SDS-PAGE, 31P NMR, ESI-MS, ESI-FTICR-MS, Western blotting, composition analysis, genetic methods