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
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.