బయోకెమిస్ట్రీ & అనలిటికల్ బయోకెమిస్ట్రీ

నైరూప్య

Human Odorant Binding Protein 2a has Two Affinity States and is Capable of Binding Some Uremic Toxins

Whitson KB and Whitson SR

Human odorant binding proteins (OBPs) are lipocalins proposed to function by carrying small molecules through aqueous environments to olfactory receptors. In contrast to previous reports, results from fluorescence assays herein show that ligands bind to OBP-2a with two affinities, one with a micromolar and one with a nanomolar equilibrium dissociation constant. Computational modeling of the protein reveals these states could be associated with two binding sites for hydrophobic and/or aromatic molecules, and is not dependent on functional groups such as aldehyde moieties. Small-molecule hydrophobic uremic toxins like p-cresol were found to effectively compete for binding to OBP-2a nearly as well as traditional odorants like vanillin. The results support a possible molecular mechanism for interference of uremic toxins that could result in the impaired olfactory sensitivity described for patients with advanced renal disease.