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 ?3,?6-mannopentaose (Man?(1-3)[Man?(1-3)[Man?(1-6)]Man?(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.

SUBMITTER: Koharudin LM 

PROVIDER: S-EPMC3154684 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature