title: Sampling of Glycan-Bound Conformers by the Anti-HIV Lectin Oscillatoria agardhii agglutinin in the Absence of Sugar.
abstract: Lectins from different sources have been shown to interfere with HIV infection by binding to the sugars of viral-envelope glycoproteins. Three-dimensional atomic structures of a number of HIV-inactivating lectins have been determined, both as free proteins and in glycan-bound forms. However, details on the mechanism of recognition and binding to sugars are elusive. Herein we focus on the anti-HIV lectin OAA from Oscillatoria agardhii: We show that in the absence of sugars in solution, both the sugar-free and sugar-bound protein conformations that were observed in the X-ray crystal structures exist as conformational substates. Our results suggest that glycan recognition occurs by conformational selection within the ground state; this model differs from the popular "excited-state" model. Our findings provide further insight into molecular recognition of the major receptor on the HIV virus by OAA. These details can potentially be used for the optimization and/or development of preventive anti-HIV therapeutics.
authors: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany).
authors: Marta G
authors: MG
authors: Carneiro
authors: Department of Structural Biology, University of Pittsburgh School of Medicine, 1050 Biomedical Science Tower 3, 3501 5th Avenue, Pittsburgh, PA 15260 (USA).
authors: Leonardus M I
authors: LM
authors: Koharudin
authors: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany).|Present address: St. Jude Children's Research Hospital, Department of Structural Biology, 262 Danny Thomas Place, Memphis, TN 38105 (USA).
authors: David
authors: D
authors: Ban
authors: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany).
authors: T Michael
authors: TM
authors: Sabo
authors: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany).
authors: Pablo
authors: P
authors: Trigo-Mourino
authors: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany).|Present address: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel (Switzerland).
authors: Adam
authors: A
authors: Mazur
authors: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany).
authors: Christian
authors: C
authors: Griesinger
authors: Department of Structural Biology, University of Pittsburgh School of Medicine, 1050 Biomedical Science Tower 3, 3501 5th Avenue, Pittsburgh, PA 15260 (USA).
authors: Angela M
authors: AM
authors: Gronenborn
authors: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany). dole@nmr.mpibpc.mpg.de.
authors: Donghan
authors: D
authors: Lee
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006678:HIV / Q000378:metabolism; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D054300:Oscillatoria / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D002241:Carbohydrates; D037102:Lectins; D011134:Polysaccharides; D014759:Viral Envelope Proteins
keywords: NMR spectroscopy; anti-HIV lectins; conformational selection; ground state; proteins