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

FEBS J. 2013 May;280(9):2056-67. doi: 10.1111/febs.12229. Epub 2013 Apr 2.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Agglutinins / chemistry*
  • Agglutinins / pharmacology
  • Amino Acid Sequence
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / pharmacology
  • Binding Sites
  • Burkholderia*
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Cell Line
  • Conserved Sequence
  • Crystallography, X-Ray
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • Humans
  • Hydrogen Bonding
  • Inhibitory Concentration 50
  • Mannans / chemistry
  • Mannose-Binding Lectins / chemistry*
  • Mannose-Binding Lectins / pharmacology
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary

Substances

  • Agglutinins
  • Anti-HIV Agents
  • Bacterial Proteins
  • Mannans
  • Mannose-Binding Lectins

Associated data

  • PDB/4GK9
  • PDB/4GU8