New Proluciferin Substrates for Human CYP4 Family Enzymes.
CYP4Z1
Cytochrome P450
Docking
Fission yeast
Homo sapiens
Pharmacology
Proluciferin
Site of metabolism prediction
Journal
Applied biochemistry and biotechnology
ISSN: 1559-0291
Titre abrégé: Appl Biochem Biotechnol
Pays: United States
ID NLM: 8208561
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
03
03
2020
accepted:
16
07
2020
pubmed:
2
9
2020
medline:
27
5
2021
entrez:
2
9
2020
Statut:
ppublish
Résumé
We report the synthesis of seven new proluciferins for convenient activity determination of enzymes belonging to the cytochrome P450 (CYP) 4 family. Biotransformation of these probe substrates was monitored using each of the twelve human CYP4 family members, and eight were found to act at least on one of them. For all substrates, activity of CYP4Z1 was always highest, while that of CYP4F8 was always second highest. Site of metabolism (SOM) predictions involving SMARTCyp and docking experiments helped to rationalize the observed activity trends linked to substrate accessibility and reactivity. We further report the first homology model of CYP4F8 including suggested substrate recognition residues in a catalytically competent conformation accessed by replica exchange solute tempering (REST) simulations.
Identifiants
pubmed: 32869209
doi: 10.1007/s12010-020-03388-6
pii: 10.1007/s12010-020-03388-6
doi:
Substances chimiques
Thiazoles
0
Aryl Hydrocarbon Hydroxylases
EC 1.14.14.1
CYP4F8 protein, human
EC 1.14.14.1
CYP4Z1 protein, human
EC 1.14.14.1
Cytochrome P450 Family 4
EC 1.14.14.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
218-237Références
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