Sialic acid mutarotation is catalyzed by the Escherichia coli beta-propeller protein YjhT.
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.
Department of Biology (Area 10), York Structural Biology Laboratory, University of York, York YO10 5YW, United Kingdom.
Emmanuele
E
Severi
Axel
A
Müller
Jennifer R
JR
Potts
Andrew
A
Leech
David
D
Williamson
Keith S
KS
Wilson
Gavin H
GH
Thomas
D002238:Carbohydrate Epimerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D018360:Crystallography, X-Ray; D048168:Escherichia coli K12 / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D029968:Escherichia coli Proteins; D037521:Virulence Factors; C527929:YjhT protein, E coli; D002238:Carbohydrate Epimerases; C019646:aldose 1-epimerase; D019158:N-Acetylneuraminic Acid