A bifunctional O-antigen polymerase structure reveals a new glycosyltransferase family

Nat Chem Biol. 2020 Apr;16(4):450-457. doi: 10.1038/s41589-020-0494-0. Epub 2020 Mar 9.

Abstract

Lipopolysaccharide O-antigen is an attractive candidate for immunotherapeutic strategies targeting antibiotic-resistant Klebsiella pneumoniae. Several K. pneumoniae O-serotypes are based on a shared O2a-antigen backbone repeating unit: (→ 3)-α-Galp-(1 → 3)-β-Galf-(1 →). O2a antigen is synthesized on undecaprenol diphosphate in a pathway involving the O2a polymerase, WbbM, before its export by an ATP-binding cassette transporter. This dual domain polymerase possesses a C-terminal galactopyranosyltransferase resembling known GT8 family enzymes, and an N-terminal DUF4422 domain identified here as a galactofuranosyltransferase defining a previously unrecognized family (GT111). Functional assignment of DUF4422 explains how galactofuranose is incorporated into various polysaccharides of importance in vaccine production and the food industry. In the 2.1-Å resolution structure, three WbbM protomers associate to form a flattened triangular prism connected to a central stalk that orients the active sites toward the membrane. The biochemical, structural and topological properties of WbbM offer broader insight into the mechanisms of assembly of bacterial cell-surface glycans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Amino Acid Sequence
  • Cell Membrane / metabolism
  • Glycosyltransferases / metabolism*
  • Glycosyltransferases / physiology
  • Hexosyltransferases
  • Klebsiella pneumoniae / metabolism
  • Lipopolysaccharides / chemistry
  • O Antigens / metabolism*
  • O Antigens / ultrastructure*
  • Polysaccharides, Bacterial / chemistry

Substances

  • ATP-Binding Cassette Transporters
  • Lipopolysaccharides
  • O Antigens
  • Polysaccharides, Bacterial
  • Glycosyltransferases
  • Hexosyltransferases
  • O-antigen polymerase