Abstract:
Serum Paraoxonase-1(PON1) is a hydrolytic enzyme which is closely
associated with High-density lipoprotein (HDL). Even though recent studies
have shown that these polymorphisms can cause the lowering of the activity
of this enzyme, the mechanism of protein–HDL interaction is not clearly
understood. Thus, this study was mainly focused on investigating the
structural changes associated with Glutamine/Arginine polymorphisms at
position 192 using molecular dynamics (MD) simulations. Accordingly, our
main objectives were to model PON1 in lipid bilayer to understand the correct
orientation and to identify the structural changes of the protein due to the
polymorphism at position 192 using MD snapshots. The CHARMM GUI web
server was used to model complexes with PON1 and lipid bilayer and 200 ns
MD run was performed using AMBER 16 software. One lipid-unbound and
three lipid-bound systems were investigated. Seven different substrates were
docked to understand the different activities of the enzyme. Out of them 7-odiethylphosphoryl-
3-cyano-7-hydroxycoumarin (DepCyc) showed the highest
binding affinity. The binding pockets of lipid-bound Q192 and R192 were
observed to be larger than that of lipid-bound K192. This difference in the
volume of binding pockets allowed the substrate selectivity of the enzyme.
