Functional interactions of adrenodoxin with several human mitochondrial cytochrome P450 enzymes.
Adrenodoxin
CYP
Cytochrome P450
NADPH-Adrenodoxin reductase
NADPH-P450 reductase
Steroid biosynthesis
Journal
Archives of biochemistry and biophysics
ISSN: 1096-0384
Titre abrégé: Arch Biochem Biophys
Pays: United States
ID NLM: 0372430
Informations de publication
Date de publication:
15 11 2020
15 11 2020
Historique:
received:
06
07
2020
revised:
11
09
2020
accepted:
12
09
2020
pubmed:
28
9
2020
medline:
16
12
2020
entrez:
27
9
2020
Statut:
ppublish
Résumé
Seven of the 57 human cytochrome P450 (P450) enzymes are mitochondrial and carry out important reactions with steroids and vitamins A and D. These seven P450s utilize an electron transport chain that includes NADPH, NADPH-adrenodoxin reductase (AdR), and adrenodoxin (Adx) instead of the diflavin NADPH-P450 reductase (POR) used by the other P450s in the endoplasmic reticulum. Although numerous studies have been published involving mitochondrial P450 systems, the experimental conditions vary considerably. We compared human Adx and bovine Adx, a commonly used component, and found very similar catalytic activities in reactions catalyzed by human P450s 11B2, 27A1, and 27C1. Binding constants of 6-200 nM were estimated for Adx binding to these P450s using microscale thermophoresis. All P450 catalytic reactions were saturated at 10 μM Adx, and higher concentrations were not inhibitory up to at least 50 μM. Collectively these studies demonstrate the tight binding of Adx (both human and bovine) to AdR and to several mitochondrial P450s and provide guidance for optimization of Adx-dependent P450 reactions.
Identifiants
pubmed: 32980349
pii: S0003-9861(20)30605-6
doi: 10.1016/j.abb.2020.108596
pmc: PMC7863566
mid: NIHMS1665187
pii:
doi:
Substances chimiques
Mitochondrial Proteins
0
Adrenodoxin
12687-22-8
Cytochrome P-450 Enzyme System
9035-51-2
Ferredoxin-NADP Reductase
EC 1.18.1.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
108596Subventions
Organisme : NIAMS NIH HHS
ID : F31 AR077386
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM118122
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007028
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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