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Published on: October 3, 2018
Slow binding modulation of paraoxonase 1 activity with terbium ions
Janez Smerkolj1, Miha Bahun2, Nataša Poklar Ulrih2
1University of Ljubljana, Faculty of Medicine, Institute of Biochemistry and Molecular Genetics, Vrazov trg 2, 1000, Ljubljana, Slovenia.
None:
Paraoxonase 1 (PON1) is a metalloenzyme that requires calcium ions at both catalytic and structural binding sites to hydrolyze the substrates. The enzyme is efficiently inhibited by several metal ions, especially transition metals, which tend to bind non-specifically to oxygen, nitrogen, and sulfur ligands of amino acid residues on the PON1 surface. In contrast, several lanthanide ions can specifically replace isomorphous Ca2+ ions from many protein binding sites, making them among the most potent metal inhibitors of PON1. However, the exact kinetic effects of lanthanides on PON1 activity are not well understood. Therefore, we investigated the inhibitory effects of Tb3+ ions on recombinant PON1 (rePON1) to elucidate how Tb3+ binding modulates its enzymatic activity. Our results reveal that Tb3+ functions as a slow-binding, reversible inhibitor of rePON1's lactonase activity through a sequential, two-step mechanism involving both metal-binding sites.
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