Distinct affinity and effector residues in the binding site for a regulatory ligand. The mitochondrial uncoupling protein as a model.

A hypothesis concerning two distinct classes of amino acid residues in some regulatory binding sites is proposed. The "affinity residues" are those that are unable to transduce the ligand information signal but are responsible for overcoming the barrier for the attachment of a ligand to its binding site while the "effector residues" transfer the binding signal to the other functional part of the protein, which then undergoes a non-equilibrium energetic cycle induced by interaction with the ligand. As an example, the purine nucleotide inhibition of H+ transport through the uncoupling protein of brown adipose tissue mitochondria is discussed; there is a concentration range in which the nucleotide is bound but does not inhibit H+ transport. This is interpreted in terms of inaccessibility of the effector residues inducing H+ transport inhibition below a certain threshold concentration.