Analysis of 7-transmembrane receptors (7TMRs) determined that receptor classification according to ligand size conforms to the phylogenetic analysis of receptor sequences revealed in the human genome, allowing functional genomic interpretations to be made and the deorphanization of novel receptors to be attempted. The structural flexibility of membrane receptors and the disposition of cysteine residues suggest a mechanism of receptor activation through redox control that satisfies the broad range of binding and activation modalities of 7TMR ligands. Evidence from the mapping of ligand templates, the performance of disparate biochemical assays, and the realization that smell molecules are the "lowest common denominator" agonists for 7TMRs all support this molecular mechanism of ligand binding and receptor activation. If this activation step can be confirmed unequivocally, then understanding the physicochemical mechanisms of receptor activation will have profound consequences for drug discovery initiatives.

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