Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

Acta Crystallogr D Biol Crystallogr. 2014 Jul;70(Pt 7):1801-11. doi: 10.1107/S139900471400830X. Epub 2014 Jun 24.

Abstract

Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states.

Keywords: molecular mimicry; sialic acid-binding proteins; structure binding.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • Binding Sites
  • Calorimetry
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Fusobacterium nucleatum / metabolism
  • Molecular Sequence Data
  • N-Acetylneuraminic Acid / metabolism*
  • Pasteurella multocida / metabolism
  • Periplasm / metabolism*
  • Polymerase Chain Reaction
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Thermodynamics
  • Vibrio cholerae / metabolism

Substances

  • Bacterial Proteins
  • DNA Primers
  • N-Acetylneuraminic Acid

Associated data

  • PDB/4MAG
  • PDB/4MMP
  • PDB/4MNP