Identification and Role of a 6‐Deoxy‐4‐Keto‐Hexosamine in the Lipopolysaccharide Outer Core of Yersinia enterocolitica Serotype O:3

• Published in: Chemistry : a European journal Vol. 15; no. 38; pp. 9747 - 9754
• Main Authors: Pinta, Elise, Duda, Katarzyna A., Hanuszkiewicz, Anna, Kaczyński, Zbigniew, Lindner, Buko, Miller, Wayne L., Hyytiäinen, Heidi, Vogel, Christian, Borowski, Sabine, Kasperkiewicz, Katarzyna, Lam, Joseph S., Radziejewska‐Lebrecht, Joanna, Skurnik, Mikael, Holst, Otto
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 28.09.2009
• Subjects: Bacterial Proteins - metabolism; Bacteriophages; Biological; biosynthesis; Cationic; Electrophoresis, Capillary; Enzymes; hexosamines; Hexosamines - biosynthesis; Hexosamines - chemistry; Hexosamines - physiology; Hydration; lipopolysaccharides; Lipopolysaccharides - chemistry; Peptides; receptors; Serotyping; structural biology; Sugars; Yersinia enterocolitica; Yersinia enterocolitica - chemistry
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200901255

The outer core (OC) region of Yersinia enterocolitica serotype O:3 lipopolysaccharide is a hexasaccharide essential for the integrity of the outer membrane. It is involved in resistance against cationic antimicrobial peptides and plays a role in virulence during early phases of infection. We show here that the proximal residue of the OC hexasaccharide is a rarely encountered 4‐keto‐hexosamine, 2‐acetamido‐2,6‐dideoxy‐D‐xylo‐hex‐4‐ulopyranose (Sugp) and that WbcP is a UDP‐GlcNAc‐4,6‐dehydratase enzyme responsible for the biosynthesis of the nucleotide‐activated form of this rare sugar converting UDP‐2‐acetamido‐2‐deoxy‐D‐glucopyranose (UDP‐D‐GlcpNAc) to UDP‐2‐acetamido‐2,6‐dideoxy‐D‐xylo‐hex‐4‐ulopyranose (UDP‐ Sugp). In an aqueous environment, the 4‐keto group of this sugar was present in the 4‐dihydroxy form, due to hydration. Furthermore, evidence is provided that the axial 4‐hydroxy group of this dihydroxy function was crucial for the biological role of the OC, that is, in the bacteriophage and enterocoliticin receptor structure and in the epitope of a monoclonal antibody. Explore the outer limits! The outer core (OC) of Yersinia enterocolitica O:3 lipopolysaccharide is important in early phases of intestinal infection. 2‐Acetamido‐2,6‐dideoxy‐D‐xylo‐hex‐4‐ulopyranose (Sugp; see figure) was identified as its proximal residue. Its 4‐keto group changed to the 4‐dihydroxy form in aqueous environments, which was crucial for the biological role of the OC as a bacteriophage and enterocoliticin receptor, and in the OC epitope of a monoclonal antibody.