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Updated: Dec 26, 2025

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
Isoleucine Residues Determine Chiral Discrimination of Odorant-Binding Protein
Valeriia Zaremska1, Jiajun Tan1,2, Sierin Lim1,2
1Biosensor Technologies, Austrian Institute of Technology GmbH, Konrad-Lorenz Straße, 24, 3430, Tulln, Austria.
Abstract:
Enzymes, receptors, and carrier proteins discriminate between enantiomers of natural and synthetic chemicals. Whereas the structural details of this phenomenon have been investigated in enzymes and receptors, much less is known for carrier proteins of hydrophobic ligands, particularly concerning the contribution of asymmetric centers in the side chains of amino acids to chirally selective binding. Working with a pig odorant-binding protein, we have found that the replacement of either one or both isoleucine residues in the binding pocket by leucines abolishes discrimination of menthol and carvone enantiomers. The results indicate that isoleucines are crucial for chiral discrimination of hydrophobic ligands, and that asymmetry in the side chain may be as important as the overall asymmetry of the protein. The results provide suggestions and guidelines for improving chiral selectivity of binding proteins and enzymes, with consequent applications in the production of enantiomerically pure drugs.
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