¹Department of Biochemistry, Faculty of Pharmacy, Marmara University, İstanbul, TURKEY
²Department of Biochemistry, Faculty of Pharmacy, Fenerbahçe University, İstanbul, TURKEY DOI : 10.29228/jrp.2022.00 Protein disulfide isomerase (PDI), a multifunctional protein plays an important role as oxidoreductase, isomerase and chaperone in the cell. Prior studies have identified PDI is highly expressed in many different cancer types and presented as a new potential target for cancer treatment. Here, we investigated vitamin D and its analogue paricalcitol in silico interaction of the human PDI and inhibition of PDI reductase activity in vitro. We observed a non-covalent mechanism where the main skeleton of the vitamin D3 and paricalcitol structure is located at the hydrophobic site in the b’ domain of PDI and forms a hydrogen bond with a residue (His138) in this domain. They also form multiple weak hydrophobic interactions with various chemical groups of the b’ subunit. For the first time, we demonstrate that 1,25- dihydroxyvitamin D3 (1α,25(OH)2 vitamin D3) and paricalcitol inhibit the PDI reductase activity in vitro and their IC50 values are 20.79±1.43 nmol/L and 32.82±3.15 nmol/L respectively. The two compounds can also block the denitrosation activity of PDI. Keywords : Protein disulfide isomerase; paricalcitol; vitamin D3; molecular docking; activity of enzymes