Sialic acid mutarotation is catalyzed by the Escherichia coli beta-propeller protein YjhT

J Biol Chem. 2008 Feb 22;283(8):4841-9. doi: 10.1074/jbc.M707822200. Epub 2007 Dec 5.

Abstract

The acquisition of host-derived sialic acid is an important virulence factor for some bacterial pathogens, but in vivo this sugar acid is sequestered in sialoconjugates as the alpha-anomer. In solution, however, sialic acid is present mainly as the beta-anomer, formed by a slow spontaneous mutarotation. We studied the Escherichia coli protein YjhT as a member of a family of uncharacterized proteins present in many sialic acid-utilizing pathogens. This protein is able to accelerate the equilibration of the alpha- and beta-anomers of the sialic acid N-acetylneuraminic acid, thus describing a novel sialic acid mutarotase activity. The structure of this periplasmic protein, solved to 1.5A resolution, reveals a dimeric 6-bladed unclosed beta-propeller, the first of a bacterial Kelch domain protein. Mutagenesis of conserved residues in YjhT demonstrated an important role for Glu-209 and Arg-215 in mutarotase activity. We also present data suggesting that the ability to utilize alpha-N-acetylneuraminic acid released from complex sialoconjugates in vivo provides a physiological advantage to bacteria containing YjhT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Epimerases / chemistry*
  • Carbohydrate Epimerases / genetics
  • Carbohydrate Epimerases / metabolism
  • Catalysis
  • Crystallography, X-Ray
  • Escherichia coli K12 / enzymology*
  • Escherichia coli K12 / genetics
  • Escherichia coli K12 / pathogenicity
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • N-Acetylneuraminic Acid / chemistry
  • N-Acetylneuraminic Acid / genetics
  • N-Acetylneuraminic Acid / metabolism
  • Protein Structure, Tertiary
  • Virulence Factors / chemistry*
  • Virulence Factors / genetics
  • Virulence Factors / metabolism

Substances

  • Escherichia coli Proteins
  • Virulence Factors
  • YjhT protein, E coli
  • Carbohydrate Epimerases
  • aldose 1-epimerase
  • N-Acetylneuraminic Acid

Associated data

  • PDB/2UVK