Koeksal, Muhammed MuratSekerler, TurgutSener, Azize2025-04-112025-04-1120252630-634410.12991/jrespharm.1626221https://doi.org/10.12991/jrespharm.1626221Protein 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 D(3 )ans paricalcitol sturcture is located at the hydrophobic site in the b' domain of PDI and forms a hydrogen bond with a residue (His138) in tihs 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 D-3 (1 alpha,25(OH)(2) vitamin D-3) and paricalcitol inhibit the PDI reductase activity in vitro and their IC50 values are 20.79 +/- 1.43 nmol/L and 32.83 +/- 3.15 nmol/L respectively. The two compounds can also block the denistrosation activity of PDI.eninfo:eu-repo/semantics/openAccessProtein Disulfide IsomeraseParicalcitolVitamin D3Molecular DockingActivity Of EnzymesArticleN/AQ42912029WOS:001489648200003