posted on 2014-11-17, 00:00authored byJilai Li, Ulf Ryde
There are three families of mononuclear
molybdenum enzymes that catalyze oxygen atom transfer (OAT) reactions,
named after a typical example from each family, viz., dimethyl sulfoxide
reductase (DMSOR), sulfite oxidase (SO), and xanthine oxidase (XO).
These families differ in the construction of their active sites, with
two molybdopterin groups in the DMSOR family, two oxy groups in the
SO family, and a sulfido group in the XO family. We have employed
density functional theory calculations on cluster models of the active
sites to understand the selection of molybdenum ligands in the three
enzyme families. Our calculations show that the DMSOR active site
has a much stronger oxidative power than the other two sites, owing
to the extra molybdopterin ligand. However, the active sites do not
seem to have been constructed to make the OAT reaction as exergonic
as possible, but instead to keep the reaction free energy close to
zero (to avoid excessive loss of energy), thereby making the reoxidation
(SO and XO) or rereduction of the active sites (DMSOR) after the OAT
reaction facile. We also show that active-site models of the three
enzyme families can all catalyze the reduction of DMSO and that the
DMSOR model does not give the lowest activation barrier. Likewise,
all three models can catalyze the oxidation of sulfite, provided that
the Coulombic repulsion between the substrate and the enzyme model
can be overcome, but for this harder reaction, the SO model gives
the lowest activation barrier, although the differences are not large.
However, only the XO model can catalyze the oxidation of xanthine,
owing to its sulfido ligand.