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

Curr Opin Struct Biol. 2019 Dec:59:29-37. doi: 10.1016/j.sbi.2019.01.019. Epub 2019 Mar 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acids / chemistry*
  • Catalytic Domain*
  • Flavins / chemistry*
  • Heme / chemistry*
  • Mixed Function Oxygenases / chemistry*
  • Molecular Conformation
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation*
  • Molecular Structure
  • Protein Binding

Substances

  • Amino Acids
  • Flavins
  • Heme
  • Mixed Function Oxygenases