New Proluciferin Substrates for Human CYP4 Family Enzymes

Jingyao Liu, David Machalz, Gerhard Wolber, Erik J. Sorensen, Matthias Bureik

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalApplied Biochemistry and Biotechnology
DOIs
StateAccepted/In press - 2020

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology

Keywords

  • CYP4Z1
  • Cytochrome P450
  • Docking
  • Fission yeast
  • Homo sapiens
  • Pharmacology
  • Proluciferin
  • Site of metabolism prediction

Fingerprint Dive into the research topics of 'New Proluciferin Substrates for Human CYP4 Family Enzymes'. Together they form a unique fingerprint.

  • Cite this