Structure of a metal-independent bacterial glycosyltransferase that catalyzes the synthesis of histo-blood group A antigen

Sci Rep. 2012:2:940. doi: 10.1038/srep00940. Epub 2012 Dec 7.

Abstract

Histo-blood group antigens (HBGAs) are a source of antigenic variation between individuals that modulates resistance and susceptibility to pathogens and is a barrier to the spread of enveloped viruses. HBGAs are also produced by a few prokaryotes where they are synthesized by glycosyltransferases (GTs) related to human HBGA synthases. Here we report the first structure of a bacterial GT of this family, from an intestinal resident, Bacteroides ovatus. Unlike its mammalian homologues and other GTs with similar folds, this protein lacks a metal-binding Asp-X-Asp motif and is fully active in the absence of divalent metal ions, yet is strikingly similar in structure and in its interactions with substrates to structurally characterized mammalian metal-dependent mammalian homologues. This shows how an apparently major divergence in catalytic properties can be accommodated by minor structural adjustments and illustrates the structural underpinnings of horizontal transfer of a functional gene from prokaryotes to vertebrates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ABO Blood-Group System / immunology
  • ABO Blood-Group System / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Bacteroides / enzymology*
  • Binding Sites
  • Biocatalysis
  • Crystallography, X-Ray
  • Glycosyltransferases / chemistry
  • Glycosyltransferases / metabolism*
  • Humans
  • Metals / chemistry*
  • Protein Structure, Tertiary
  • Substrate Specificity
  • Thermodynamics

Substances

  • ABO Blood-Group System
  • Bacterial Proteins
  • Metals
  • Glycosyltransferases

Associated data

  • PDB/4AYJ
  • PDB/4AYL