Beyond active site residues: overall structural dynamics control catalysis in flavin-containing and heme-containing monooxygenases

Maximilian J. L. J. Fürst, Filippo Fiorentini, Marco W. Fraaije*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)
197 Downloads (Pure)

Abstract

Monooxygenases (MOs) face the challenging reaction of an organic target, oxygen and a cofactor – most commonly heme or flavin. To correctly choreograph the substrates spatially and temporally, MOs evolved a variety of strategies, which involve structural flexibility. Besides classical domain and loop movements, flavin-containing MOs feature conformational changes of their flavin prosthetic group and their nicotinamide cofactor. With similar mechanisms emerging in various subclasses, their generality and involvement in selectivity are intriguing questions. Cytochrome P450 MOs are often inherently plastic and large movements of individual segments throughout the entire structure occur. As these complicated and often unpredictable movements are largely responsible for substrate uptake, engineering strategies for these enzymes were mostly successful when randomly mutating residues across the entire structure.

Original languageEnglish
Pages (from-to)29-37
Number of pages9
JournalCurrent Opinion in Structural Biology
Volume59
Early online date2-Mar-2019
DOIs
Publication statusPublished - Dec-2019

Keywords

  • CRYSTAL-STRUCTURE
  • CONFORMATIONAL-CHANGE
  • DIRECTED EVOLUTION
  • OXYGEN ACTIVATION
  • MOBILE FLAVIN
  • MECHANISM
  • C4A-HYDROPEROXYFLAVIN
  • HYDROXYLASE
  • PLASTICITY
  • ALLOSTERY

Cite this