Cytochrome P450 (P450) 2J2 catalyzes
epoxidation of arachidonic acid to
eicosatrienoic acids, which are related
to a variety of diseases such as coronary
artery disease, hypertension, and
carcinogenesis. Recent experimental
data also suggest that P450 2J2 could
be a novel biomarker and a potential
target for cancer therapy. However,
the active site topology and substrate
specificity of this enzyme remain
unclear. In this study, a three-dimensional
model of human P450 2J2 was
first constructed on the basis of the
crystal structure of human P450 2C9
in complex with a substrate using
homology modeling method, and
refined by molecular dynamics simulation.
Flexible docking approaches were
then employed to dock four ligands
into the active site of P450 2J2 in
order to probe the ligand-binding
modes. By analyzing the results, active
site architecture and certain key residues
responsible for substrate specificity
were identified on the enzyme,
which might be very helpful for understanding
the enzyme’s biological role
and providing insights for designing
novel inhibitors of P450 2J2.