title: Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site.
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.
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065, India.
authors.forename: Thanuja
authors.initials: T
authors.lastname: Gangi Setty
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Cho
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065, India.
authors.forename: Sowmya
authors.initials: S
authors.lastname: Govindappa
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Apicella
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065, India.
authors.forename: S
authors.initials: S
authors.lastname: Ramaswamy
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002151:Calorimetry; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D016967:Fusobacterium nucleatum / Q000378:metabolism; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D016979:Pasteurella multocida / Q000378:metabolism; D019897:Periplasm / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D014734:Vibrio cholerae / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; D019158:N-Acetylneuraminic Acid
keywords: molecular mimicry; sialic acid-binding proteins; structure binding