Burkholderia oklahomensis agglutinin is a canonical two‐domain OAA‐family lectin: structures, carbohydrate binding and anti‐HIV activity

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. Database The atomic coordinates and structure factors for ligand‐bound and ligand‐free BOA have been deposited into the Protein Data Bank under accession numbers 4GK9 and 4GU8, respectively. Burkholderia oklahomensis EO147 agglutinin (BOA) is a two‐domain member of the OAA family of anti‐HIV lectins. In this work, we present the x‐ray crystal structures of BOA in the ligand‐free state and bound to four molecules of 3α,6α‐mannopentaose. Additionally, we characterize sugar binding via NMR spectroscopy and assay BOA's ability to block HIV entry into target cells.