Novel fold and carbohydrate specificity of the potent anti-HIV cyanobacterial lectin from Oscillatoria agardhii.
Oscillatoria agardhii agglutinin (OAA) is a recently discovered cyanobacterial lectin that exhibits potent anti-HIV activity. Up to now, only its primary structure and carbohydrate binding data have been available. To elucidate the structural basis for the antiviral mechanism of OAA, we determined the structure of this lectin by x-ray crystallography at 1.2 Å resolution and mapped the specific carbohydrate recognition sites of OAA by NMR spectroscopy. The overall architecture of OAA comprises 10 β-strands that fold into a single, compact, β-barrel-like domain, creating a unique topology compared with all known protein structures in the Protein Data Bank. OAA sugar binding was tested against Man-9 and various disaccharide components of Man-9. Two symmetric carbohydrate-binding sites were located on the protein, and a preference for Manα(1-6)Man-linked sugars was found. Altogether, our structural results explain the antiviral activity OAA and add to the growing body of knowledge about antiviral lectins.
Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
Leonardus M I
LM
Koharudin
William
W
Furey
Angela M
AM
Gronenborn
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism; D008358:Mannose / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D054300:Oscillatoria / Q000737:chemistry*; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary
D019380:Anti-HIV Agents; D002241:Carbohydrates; D037102:Lectins; D008358:Mannose