Cytochromes P450

Guengerich, F. Peter

doi:10.1002/9783527630905.ch2

Cited by 8 publications

(7 citation statements)

References 207 publications

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“…They are membrane-localized monooxygenase enzymes to catalyze extremely diverse processes by activation and heterolytic cleavage of oxygen into the water molecule. The reduced P450 enzyme has a light absorption spectrum at 450nm where carbon monoxide binds to the haeme moiety [5]. Lengths of the CYPs are in the range of 475-550 amino acids and their nomenclatures in plant are based on the protein sequence identity, phylogeny and gene organization.…”

Section: Introductionmentioning

confidence: 99%

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Evolutionary and Functional Characterization of Cytochrome P450 in Cotton Reveal the Role of Subgenome Expression of GhCYP78A for Cotton Fiber Initiation

Verma¹,

Khatoon²,

Sawant³

et al. 2022

Preprint

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Cytochrome P450 (CYPs) is a functionally diversified third-largest gene family that exploded in the plant kingdom. Their role in different organ development has been illustrated by the intervention of phytohormone. Cotton is a model organism for cell differentiation and cell elongation. To decipher the participation of CYPs in different cotton fiber developmental stages, we identified and characterized 2460 CYPs in three diploids and two allotetraploid cottons. Furthermore, In-silico expression and cluster analysis of cotton CYPs was conducted to distinguish the fiber stage-specific clusters that have the determining role in different stages of fiber development. The subgenome expression of two conserved Gossypium hirsutum CYPs, namely, GhCYP78A197 and GhCYP78A198 contributed to fiber initiation at an early stage of fiber development, governed by the co-occurrence of TATA and MYB TFs binding sites. Coexpression network partners of these two GhCYP78A annotated as auxin, kinases, chromatin remodeler, epigenetic regulator and cyclin-related genes that possibly induce the endoreduplication and cell proliferation for fiber cell initiation to define the high yield and biomass.

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Section: Introductionmentioning

confidence: 99%

“…Lengths of the CYPs are in the range of 475-550 amino acids and their nomenclatures in plant are based on the protein sequence identity, phylogeny and gene organization. The 40% identity criteria have been set up for the categorization under the same family while at least 55% identity is required for subfamily assignment [5].…”

Section: Introductionmentioning

confidence: 99%

Evolutionary and Functional Characterization of Cytochrome P450 in Cotton Reveal the Role of Subgenome Expression of GhCYP78A for Cotton Fiber Initiation

Verma¹,

Khatoon²,

Sawant³

et al. 2022

Preprint

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“…Cytochrome P450 enzymes (CYPs) are important in the oxidative biotransformation of endogenous compounds and xenobiotics including drugs and environmental chemicals [ 8 , 9 , 10 ]. Drug–drug interactions that affect CYP activity can cause major problems in patients who are undergoing multi-drug treatment or who consume certain foods: the resulting enzyme inhibition can increase the risk of adverse reactions or reduce the effectiveness of prodrugs.…”

Section: Introductionmentioning

confidence: 99%

Influence of Amlodipine Enantiomers on Human Microsomal Cytochromes P450: Stereoselective Time-Dependent Inhibition of CYP3A Enzyme Activity

2017

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Amlodipine (AML) is available as a racemate, i.e., a mixture of R- and S-enantiomers. Its inhibitory potency towards nine cytochromes P450 (CYP) was studied to evaluate the drug–drug interactions between the enantiomers. Enzyme inhibition was evaluated using specific CYP substrates in human liver microsomes. With CYP3A, both enantiomers exhibited reversible and time-dependent inhibition. S-AML was a stronger reversible inhibitor of midazolam hydroxylation: the Ki values of S- and R-AML were 8.95 µM, 14.85 µM, respectively. Computational docking confirmed that the enantiomers interact differently with CYP3A: the binding free energy of S-AML in the active site was greater than that for R-AML (−7.6 vs. −6.7 kcal/mol). Conversely, R-AML exhibited more potent time-dependent inhibition of CYP3A activity (KI 8.22 µM, Kinact 0.065 min−1) than S-AML (KI 14.06 µM, Kinact 0.041 min−1). R-AML was also a significantly more potent inhibitor of CYP2C9 (Ki 12.11 µM/S-AML 21.45 µM) and CYP2C19 (Ki 5.97 µM/S-AML 7.22 μM. In conclusion, results indicate that clinical use of S-AML has an advantage not only because of greater pharmacological effect, but also because of fewer side effects and drug–drug interactions with cytochrome P450 substrates due to absence of R-AML.

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“…The role in the liver is 25-hydroxylation of the biologically inert vitamins D 2 and D 3 , the first and obligatory step in the production of the active form of these vitamins (69). Although a number of other P450 enzymes (CYP27A1, CYP2C11, and CYP2J3) can 25-hydroxylate vitamin D 3 , available evidence points to CYP2R1 as the major vitamin D 3 25-hydroxylase (71-73). Mutations in CYP2R1 lead to low serum levels of 25-hydroxyvitamin D 3 and are associated with rickets (softening and weakening of bones in children, leading to bone deformities and fractures).…”

Section: P450-dependent Diseases Of Activation and Inactivation Of VImentioning

confidence: 99%

“…Although a number of other P450 enzymes (CYP27A1, CYP2C11, and CYP2J3) can 25-hydroxylate vitamin D 3 , available evidence points to CYP2R1 as the major vitamin D 3 25-hydroxylase (71-73). Mutations in CYP2R1 lead to low serum levels of 25-hydroxyvitamin D 3 and are associated with rickets (softening and weakening of bones in children, leading to bone deformities and fractures). CYP2R1 deficiency is designated as vitamin D-dependent rickets type 1B (MIM 600081) (71, 74 -76).…”

Section: P450-dependent Diseases Of Activation and Inactivation Of VImentioning

confidence: 99%