Catalytic reaction mechanisms of nonheme iron dioxygenases and halogenases: implications for biotechnology

Catalytic reaction mechanisms of nonheme iron dioxygenases and halogenases: implications for biotechnology

  • Datum: 12.04.2018
  • Uhrzeit: 14:00 - 15:00
  • Vortragende(r): Dr. Samuel de Visser, University of Manchester, Manchester Institute of Biotechnology, UK
  • Ort: Max-Planck-Institut Magdeburg
  • Raum: Seminarraum Wiener
  • Kontakt: matthias.stein@mpi-magdeburg.mpg.de
Catalytic reaction mechanisms of nonheme iron dioxygenases and halogenases: implications for biotechnology

Abstract

Nonheme iron hydroxylases catalyze a range of vital reactions for human health particularly related to aging. For instance, they are involved in the biosynthesis of R-4-hydroxyproline, the catabolism of cysteine as well as DNA repair mechanisms. There are many facets to the catalytic reaction mechanism of these enzymes that are still elusive. In this presentation, I will give an overview of recent quantum mechanics/molecular mechanics and density functional theory studies of our group on the mechanism and function of a nonheme iron hydroxylase (prolyl-4-hydroxylase) and a nonheme iron halogenase (hectochlorin biosynthesis protein). Both enzymes contain a nonheme iron active center that is bound to the protein through interactions with two histidine side chains and in addition have an anionic ligand: aspartate in the hydroxylases and halide in the halogenases. In both enzymes the oxidant triggers a regio- and stereospecific reaction mechanism and the calculations were focused on understanding the reactivity patterns and particularly the importance of the secondary structure of the protein to guide the regio- and stereospecific product formation through proper substrate positioning but also through electrostatic interactions. We performed detailed computational studies on the mechanisms leading to products and by-products for wildtype as well as mutants. In addition, we recently bioengineered a nonheme iron hydroxylase and managed to complete a full enantioselectivity reversal in the products.


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