Protein expression, crystallization and in-silico studies on cytochrome P450 Oxidoreductase wildtype and mutant variants

N.A.

Makale detayları

Protein expression, crystallization and in-silico studies on cytochrome P450 Oxidoreductase wildtype and mutant variants

Yazarlar:

N.A.

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Sciences

Dergi:

Journal of Research in Pharmacy Vol.28 Issue 2, pp.560-570

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001346208

pISSN:

2630-6344

Anahtar kelimeler:

Özet:

 Cytochrome P450 oxidoreductase POR is a crucial membrane-bound enzyme that facilitates the transfer of electrons to all cytochrome P450 CYP450 enzymes. Several mutations in the POR gene have been reported to cause cytochrome P450 oxidoreductase deficiency PORD, an autosomal recessive genetic disorder. This study explored the consequences of seven POR missense mutations Y181D, A287P, R457H, R498P, C569Y, Y607C, and H628P, which have been documented in PORD patients, on the structural integrity and stability of the POR enzyme in vitro. The comparison between these mutants and the wild-type POR focused on in vitro protein expression, purification, and crystallization characteristics. The mutation-induced alterations in the POR architecture significantly influenced the proteins expression and crystallization capabilities. The magnitude of these effects on the enzymes behavior varied from moderate to severe, contingent on the mutations nature and position. This research illuminates the influence of specific mutations on POR stability, underlining the necessity of understanding mutation-driven effects on enzyme stability to devise personalized therapeutic approaches for PORD patients. Future studies will involve the functional characterization of these mutant enzymes to further understand their impact on the POR enzymes activity and stability.

 Cytochrome P450 oxidoreductase POR is a crucial membrane-bound enzyme that facilitates the transfer of electrons to all cytochrome P450 CYP450 enzymes. Several mutations in the POR gene have been reported to cause cytochrome P450 oxidoreductase deficiency PORD, an autosomal recessive genetic disorder. This study explored the consequences of seven POR missense mutations Y181D, A287P, R457H, R498P, C569Y, Y607C, and H628P, which have been documented in PORD patients, on the structural integrity and stability of the POR enzyme in vitro. The comparison between these mutants and the wild-type POR focused on in vitro protein expression, purification, and crystallization characteristics. The mutation-induced alterations in the POR architecture significantly influenced the proteins expression and crystallization capabilities. The magnitude of these effects on the enzymes behavior varied from moderate to severe, contingent on the mutations nature and position. This research illuminates the influence of specific mutations on POR stability, underlining the necessity of understanding mutation-driven effects on enzyme stability to devise personalized therapeutic approaches for PORD patients. Future studies will involve the functional characterization of these mutant enzymes to further understand their impact on the POR enzymes activity and stability.

 Cytochrome P450 oxidoreductase POR is a crucial membrane-bound enzyme that facilitates the transfer of electrons to all cytochrome P450 CYP450 enzymes. Several mutations in the POR gene have been reported to cause cytochrome P450 oxidoreductase deficiency PORD, an autosomal recessive genetic disorder. This study explored the consequences of seven POR missense mutations Y181D, A287P, R457H, R498P, C569Y, Y607C, and H628P, which have been documented in PORD patients, on the structural integrity and stability of the POR enzyme in vitro. The comparison between these mutants and the wild-type POR focused on in vitro protein expression, purification, and crystallization characteristics. The mutation-induced alterations in the POR architecture significantly influenced the proteins expression and crystallization capabilities. The magnitude of these effects on the enzymes behavior varied from moderate to severe, contingent on the mutations nature and position. This research illuminates the influence of specific mutations on POR stability, underlining the necessity of understanding mutation-driven effects on enzyme stability to devise personalized therapeutic approaches for PORD patients. Future studies will involve the functional characterization of these mutant enzymes to further understand their impact on the POR enzymes activity and stability.

 Cytochrome P450 oxidoreductase POR is a crucial membrane-bound enzyme that facilitates the transfer of electrons to all cytochrome P450 CYP450 enzymes. Several mutations in the POR gene have been reported to cause cytochrome P450 oxidoreductase deficiency PORD, an autosomal recessive genetic disorder. This study explored the consequences of seven POR missense mutations Y181D, A287P, R457H, R498P, C569Y, Y607C, and H628P, which have been documented in PORD patients, on the structural integrity and stability of the POR enzyme in vitro. The comparison between these mutants and the wild-type POR focused on in vitro protein expression, purification, and crystallization characteristics. The mutation-induced alterations in the POR architecture significantly influenced the proteins expression and crystallization capabilities. The magnitude of these effects on the enzymes behavior varied from moderate to severe, contingent on the mutations nature and position. This research illuminates the influence of specific mutations on POR stability, underlining the necessity of understanding mutation-driven effects on enzyme stability to devise personalized therapeutic approaches for PORD patients. Future studies will involve the functional characterization of these mutant enzymes to further understand their impact on the POR enzymes activity and stability.

Makale detayları

Protein expression, crystallization and in-silico studies on cytochrome P450 Oxidoreductase wildtype and mutant variants

Yazarlar:

N.A.

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Sciences

Dergi:

Journal of Research in Pharmacy Vol.28 Issue 2, pp.560-570

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001346208

pISSN:

2630-6344

Cytochrome P450 oxidoreductase (POR)

cytochrome P450 oxidoreductase deficiency (PORD)

POR protein expression

POR crystallization

POR mutants

Sayı

Makale detayları

Protein expression, crystallization and in-silico studies on cytochrome P450 Oxidoreductase wildtype and mutant variants

Yazarlar: N.A.

Yayıncı: Marmara University

Ana Başlıklar: Pharmaceutical Sciences

Dergi: Journal of Research in Pharmacy Vol.28 Issue 2, pp.560-570

Belge Tipi: Makale

Yayın Tarihi: 6/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001346208

pISSN: 2630-6344

Cytochrome P450 oxidoreductase (POR)

cytochrome P450 oxidoreductase deficiency (PORD)

POR protein expression

POR crystallization

POR mutants

Sayı

Yazarlar:

N.A.

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Sciences

Dergi:

Journal of Research in Pharmacy Vol.28 Issue 2, pp.560-570

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001346208

pISSN:

2630-6344