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

TY - JOUR

T1 - Sialic acid mutarotation is catalyzed by the Escherichia coli beta-propeller protein YjhT

AU - Severi, Emmanuele

AU - Mueller, Axel

AU - Potts, Jennifer R.

AU - Leech, Andrew

AU - Williamson, David

AU - Wilson, Keith S.

AU - Thomas, Gavin H.

PY - 2008/2/22

Y1 - 2008/2/22

N2 - 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 1.5 A 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.

AB - 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 1.5 A 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.

KW - KELCH-REPEAT SUPERFAMILY

KW - HAEMOPHILUS-INFLUENZAE

KW - CRYSTAL-STRUCTURE

KW - STRUCTURAL-CHARACTERIZATION

KW - SERUM RESISTANCE

KW - VIRULENCE FACTOR

KW - NEURAMINIC ACID

KW - LIPOPOLYSACCHARIDE

KW - TRANSPORTER

KW - K-12

UR - http://www.scopus.com/inward/record.url?scp=41949134864&partnerID=8YFLogxK

U2 - 10.1074/jbc.M707822200

DO - 10.1074/jbc.M707822200

M3 - Article

SN - 0021-9258

VL - 283

SP - 4841

EP - 4849

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 8

ER -