Abstract
We present ab initio calculations on models of the “charge relay” triads Serine-Histidine-Aspartate, Cysteine-Histidine-Asparagine and Cysteine-Histidine-Aspartate. The direct calculations on double proton transfer indicate that it is significantly more favourable than single proton transfer in both serine and cysteine protease models and Asp is considerably more effective than Asn as the third member of the triad. However, correcting these proton transfer energies for known deficiencies in calculated proton affinities makes single proton transfer more likely than double proton transfer. The electrostatic potential in a-chymotrypsin makes the proton transfer more difficult, whereas that in subtilisin facilitates it. In papain, the potential favours single proton transfer, but not double proton-transfer.
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Hayes, D.M., Kollman, P.A. (1979). A Comparison of the Energetics of Proton Transfer in the Serine and Cysteine “Charge Relay” Systems and the Role of the Protein Electrostatic Potential on the Proton Transfer Energetics. In: Pullman, B. (eds) Catalysis in Chemistry and Biochemistry Theory and Experiment. The Jerusalem Symposia on Quantum Chemistry and Biochemistry, vol 12. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-9513-0_7
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