title: Burkholderia oklahomensis agglutinin is a canonical two-domain OAA-family lectin: structures, carbohydrate binding and anti-HIV activity.
abstract: Burkholderia oklahomensis EO147 agglutinin (BOA) is a 29 kDa member of the Oscillatoria agardhii agglutinin (OAA) family of lectins. Members of the OAA family recognize high-mannose glycans, and, by binding to the HIV envelope glycoprotein 120 (gp120), block the virus from binding to and entering the host cell, thereby inhibiting infection. OAA-family lectins comprise either one or two homologous domains, with a single domain possessing two glycan binding sites. We solved the structure of BOA in the ligand-free form as well as in complex with four molecules of 3α,6α-mannopentaose, the core unit of the N-linked high-mannose structures found on gp120 in vivo. This is the first structure of a double-domain OAA-family lectin in which all four binding sites are occupied by ligand. The structural details of the BOA-glycan interactions presented here, together with determination of affinity constants and HIV inactivation data, shed further light onto the structure-function relationship in this important class of anti-HIV proteins.
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Whitley
authors.forename: William
authors.initials: W
authors.lastname: Furey
authors.forename: Sireesha
authors.initials: S
authors.lastname: Kollipara
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
mesh_terms: D000373:Agglutinins / Q000737:chemistry* / Q000494:pharmacology; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D019117:Burkholderia; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002460:Cell Line; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008351:Mannans / Q000737:chemistry; D037241:Mannose-Binding Lectins / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D000373:Agglutinins; D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D008351:Mannans; D037241:Mannose-Binding Lectins