title: Structural basis of the anti-HIV activity of the cyanobacterial Oscillatoria Agardhii agglutinin.
abstract: The cyanobacterial Oscillatory Agardhii agglutinin (OAA) is a recently discovered HIV-inactivating lectin that interacts with high-mannose sugars. Nuclear magnetic resonance (NMR) binding studies between OAA and α3,α6-mannopentaose (Manα(1-3)[Manα(1-3)[Manα(1-6)]Manα(1-6)]Man), the branched core unit of Man-9, revealed two binding sites at opposite ends of the protein, exhibiting essentially identical affinities. Atomic details of the specific protein-sugar contacts in the recognition loops of OAA were delineated in the high-resolution crystal structures of free and glycan-complexed protein. No major changes in the overall protein structure are induced by carbohydrate binding, with essentially identical apo- and sugar-bound conformations in binding site 1. A single peptide bond flip at W77-G78 is seen in binding site 2. Our combined NMR and crystallographic results provide structural insights into the mechanism by which OAA specifically recognizes the branched Man-9 core, distinctly different from the recognition of the D1 and D3 arms at the nonreducing end of high-mannose carbohydrates by other antiviral lectins.
authors.affiliation: Department of Structural Biology, School of Medicine, University of Pittsburgh, Biomedical Science Tower 3, Pittsburgh, PA 15260, USA.
authors.forename: Leonardus M I
authors.initials: LM
authors.lastname: Koharudin
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
mesh_terms: D000373:Agglutinins / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000737:chemistry*; D001059:Apoproteins / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D037601:Mannose-Binding Lectin / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry; D054300:Oscillatoria; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D000373:Agglutinins; D019380:Anti-HIV Agents; D001059:Apoproteins; D001426:Bacterial Proteins; D015699:HIV Envelope Protein gp120; D037601:Mannose-Binding Lectin; D009844:Oligosaccharides; C514793:gp120 protein, Human immunodeficiency virus 1; C048068:mannopentaose