Browsing by Author "Koksal, Muhammed Murat"

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    The Effect of Vitamin D and Paricalcitol on Protein Disulfide Isomerase
    (Marmara Univ, Fac Pharmacy, 2024) Koksal, Muhammed Murat; Sekerler, Turgut; Sener, Azize
    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 1,25dihydroxyvitamin D3 (1 alpha,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.