Are inhalation anesthetics really receptor-binding drugs? : calorimetry of firefly luciferase

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Interaction modes of ligands with firefly luciferase (FFL) were investigated by calorimetry to clarify the high anesthetic sensitivity of FFL. Results of differential scanning calorimetry of FFL solutions revealed that the effect of an anesthetic chloroform on the structural stability of FFL is in direct opposition to that of the competitive inhibitor decanoic acid, and that the anesthetic sensitivity of FFL is markedly enhanced in the presence of the substrate (ATP) or decanoic acid as compared with that in the absence of the ligand. Results of isothermal titration calorimetry showed that the binding mode of an anesthetic halothane with FFL is quite different from that of decanoic acid thermodynamically. Comparing these thermal results with the structural data obtained by X-ray crystallography, we concluded that the possibility that there exist the anesthetic binding sites in FFL is very low.