Background:The Oscillatoria agardhii agglutinin homolog (OAAH) proteins constitute a novel lectin family. Results: Three-dimensional structures, carbohydrate binding specificities, and antiviral activity data for several members were determined. Conclusion: All members display potent anti-HIV activity. Significance: Our results uncovered the structural basis of protein-carbohydrate recognition in this novel lectin family and provide insights into the molecular basis of their HIV inactivation properties.
Burkholderia oklahomensis EO147 agglutinin (BOA) is a 29 kDa member of the 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 lectin in which all four binding sites are occupied by ligand. The structural details of the BOA-glycan interactions presented here, along with the determination of affinity constants and HIV inactivation data, shed further light onto the structure-function relationship in this important class of anti-HIV proteins.
Brownian dynamics (BD) simulations provide here a theoretical atomic-level treatment of the reduction of human ferric cytochrome b5 (cyt b5) by NADH-cytochrome b5 reductaste (cyt b5r) and several of its mutants. BD is used to calculate the second-order rate constant of electron transfer (ET) between the proteins for direct correlation with experiments. Interestingly, the inclusion of electrostatic forces dramatically increases the reaction rate of the native proteins despite the overall negative charge of both proteins. The role played by electrostatic charge distribution in stabilizing the ET complexes and the role of mutations of several amino acid residues in stabilizing or destabilizing the complexes are analyzed. The complex with the shortest ET reaction distance (d = 6.58 Å) from rigid body BD is further subjected to 1 ns of molecular dynamics (MD) in a periodic box of TIP3P water to produce a more stable complex allowed by flexibility and with a shorter average reaction distance d = 6.02 Å. We predict a docking model in which the following ion-ion interactions are dominant (cyt b5r/cyt b5): Lys162-Heme O1D/Lys163-Asp64/Arg91-Heme O1A/Lys125-Asp70.
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