The effect of vitamin D and paricalcitol on protein  disulfide isomerase

Turgut Şekerler; Azize Şener

Article Details

The effect of vitamin D and paricalcitol on protein disulfide isomerase

Authors:

Turgut Şekerler | Azize Şener

Publisher:

Marmara University

Main Topics:

Pharmaceutical Biochemistry

Journal:

Journal of Research in Pharmacy Vol.29 Issue 1, pp.20-29

Document Type:

Article

Publication Date:

3/2025

Document Language:

English

Document ID (Org No.):

2001339590

pISSN:

2630-6344

Keywords:

Abstract:

 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 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 D3 1a,25OH2 vitamin D3 and paricalcitol inhibit the PDI reductase activity in vitro and their IC50 values are 20.791.43 nmolL and 32.833.15 nmolL respectively. The two compounds can also block the denistrosation activity of PDI.

 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 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 D3 1a,25OH2 vitamin D3 and paricalcitol inhibit the PDI reductase activity in vitro and their IC50 values are 20.791.43 nmolL and 32.833.15 nmolL respectively. The two compounds can also block the denistrosation activity of PDI.

 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 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 D3 1a,25OH2 vitamin D3 and paricalcitol inhibit the PDI reductase activity in vitro and their IC50 values are 20.791.43 nmolL and 32.833.15 nmolL respectively. The two compounds can also block the denistrosation activity of PDI.

 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 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 D3 1a,25OH2 vitamin D3 and paricalcitol inhibit the PDI reductase activity in vitro and their IC50 values are 20.791.43 nmolL and 32.833.15 nmolL respectively. The two compounds can also block the denistrosation activity of PDI.

Article Details

The effect of vitamin D and paricalcitol on protein disulfide isomerase

Authors:

Turgut Şekerler | Azize Şener

Publisher:

Marmara University

Main Topics:

Pharmaceutical Biochemistry

Journal:

Journal of Research in Pharmacy Vol.29 Issue 1, pp.20-29

Document Type:

Article

Publication Date:

3/2025

Document Language:

English

Document ID (Org No.):

2001339590

pISSN:

2630-6344

Protein disulfide isomerase

paricalcitol

vitamin D3

molecular docking

activity of enzymes

Issues

Article Details

The effect of vitamin D and paricalcitol on protein disulfide isomerase

Authors: Turgut Şekerler | Azize Şener

Publisher: Marmara University

Main Topics: Pharmaceutical Biochemistry

Journal: Journal of Research in Pharmacy Vol.29 Issue 1, pp.20-29

Document Type: Article

Publication Date: 3/2025

Document Language: English

Document ID (Org No.): 2001339590

pISSN: 2630-6344

Protein disulfide isomerase

paricalcitol

vitamin D3

molecular docking

activity of enzymes

Issues

Authors:

Turgut Şekerler | Azize Şener

Publisher:

Marmara University

Main Topics:

Pharmaceutical Biochemistry

Journal:

Journal of Research in Pharmacy Vol.29 Issue 1, pp.20-29

Document Type:

Article

Publication Date:

3/2025

Document Language:

English

Document ID (Org No.):

2001339590

pISSN:

2630-6344