quantum mechanical/molecular mechanical dynamics analysis of the effect of metal substitution on the rate determining step in the catalytic cycle of COMT, the methyl transfer. In full accord with experimental data, Mg(II) bound to COMT is the most potent of the studied cations and it is closely followed by Fe(II), whereas Fe(III) is unable to promote catalysis. Ca(II) induces a repacking of the protein binding site, leading to a significant increase in the activation barrier and higher energy of reaction. The effect of metal substitution is different for different metals: for Fe(III) it is the electronic effect, for Ca(II) it is the effect of suboptimal protein structure |
Homo sapiens |