The complete electronic structure and mechanism of the methionine synthase process as determined by the MCSCF method

Abstract

The methionine synthase process is regenerating the methionine from cysteine in the S-adenosylmethionine cycle running throughout several interactions and electron transfers between methylcobalamin cofactor and substrates. The methionine synthase process in connection with the methionine synthase reductase process can run, in principle, unlimited number of turnovers without side products or effects. This raises questions about the energy barriers of the methionine synthase process reactions. The CASSCF geometry optimization with 13 electrons and 13 orbitals in the active zone of the methylco(II)balamin cofactor species was used to calculate the full mechanism of the methionine synthase process. We have shown that the anticipated reaction of the methionine synthase process is the cleavage of the Co-N (dimethylbenzimidazole) axial bond under the influence of the homocysteine ion and the histidine substrates. Our results also show that the active species in the methylation of homocysteine is a base-on methylco(II)balamin cofactor with the dimethylbenzimidazole ligand substituted by the histidine trans ligand. This methylation process takes place during the methylco(II)balamin cofactor interaction with the homocysteine negative ion, proving that this reaction is of SN2. We have shown that the triggering factor of this process is the initial electron transfer from a homocysteine negative ion to a base-on methylco(II)balamin-histidine cofactor particle. Another step of the methionine synthase process is the N-C(CH3) bond cleavage in the protonated 5-methyltetrahydrofolate systems under the influence of the negative total (and the atomic charges of the central part) of the co(I)balamin cofactor. Simultaneously, the cleaved methyl (+1) positive particle is leaving an electron back to tetrahydrofolate. The no energy barrier and the minimum energy of the in-vivo reaction products have been proved for all the methionine synthase process reactions. Finally, the full mechanism of the methionine synthase process has been drawn.