It is known that tyrosinase is an enzyme responsible for melanin production and has two zinc ions (or copper ions) in its active site. In recent years, we have performed an FMO calculation with FMO2-MP2/6-31G revel for tyrosinase-tyrosine complex to obtain detailed knowledge on the enzymatic reaction mechanism of tyrosinase. We found that the FMO calculation converged and is somewhat valid even for metal-containing systems (at least for the tyrosinase complex). In this paper, we carried out an FMO calculation raising the computational revel to FMO2-MP2/6-31G* and computed the inter-fragment interaction energies (IFIEs) among tyrosine, zinc ions, water molecule, and the amino acid residues in tyrosinase. The FMO computations show that two zinc ions that bind strongly to tyrosinase hold tyrosine and a water molecule in the active site of tyrosinase. It is consider that a water molecule between two zinc ions involves the oxidation reaction of tyrosine. We found that the two zinc ions and a water molecule play an essential role in reaction process.
