title: Structural insights into the anti-HIV activity of the Oscillatoria agardhii agglutinin homolog lectin family.
abstract: Oscillatoria agardhii agglutinin homolog (OAAH) proteins belong to a recently discovered lectin family. All members contain a sequence repeat of ~66 amino acids, with the number of repeats varying among different family members. Apart from data for the founding member OAA, neither three-dimensional structures, information about carbohydrate binding specificities, nor antiviral activity data have been available up to now for any other members of the OAAH family. To elucidate the structural basis for the antiviral mechanism of OAAHs, we determined the crystal structures of Pseudomonas fluorescens and Myxococcus xanthus lectins. Both proteins exhibit the same fold, resembling the founding family member, OAA, with minor differences in loop conformations. Carbohydrate binding studies by NMR and x-ray structures of glycan-lectin complexes reveal that the number of sugar binding sites corresponds to the number of sequence repeats in each protein. As for OAA, tight and specific binding to α3,α6-mannopentaose was observed. All the OAAH proteins described here exhibit potent anti-HIV activity at comparable levels. Altogether, our results provide structural details of the protein-carbohydrate interaction for this novel lectin family and insights into the molecular basis of their HIV inactivation properties.
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Leonardus M I
authors.initials: LM
authors.lastname: Koharudin
authors.forename: Sireesha
authors.initials: S
authors.lastname: Kollipara
authors.forename: Christopher
authors.initials: C
authors.lastname: Aiken
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
mesh_terms: D000373:Agglutinins / Q000737:chemistry*; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry*; D002241:Carbohydrates / Q000737:chemistry; D018360:Crystallography, X-Ray / Q000379:methods; D006678:HIV / Q000378:metabolism; D037102:Lectins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D054300:Oscillatoria / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014961:X-Ray Diffraction
chemical_list: D000373:Agglutinins; D019380:Anti-HIV Agents; D002241:Carbohydrates; D037102:Lectins; D011134:Polysaccharides; D011506:Proteins