Computational Modeling of Catalytic Mechanisms of Glycyl Radical Enzymes

In this thesis, different computational methods have been used to study the catalytic mechanisms of three glycyl radical enzymes. The mechanism of the B(12)-independent glycerol dehydratase has been elucidated by combining continuum electrostatic and density functional theory calculations. A mechanism for the dehydration of glycerol is proposed that does not involve a complex intramolecular 1→2 shift of the middle hydroxyl group, as previously suggested. Instead, the enzyme uses a pair of residues in the active site, glutamate and histidine, to facilitate direct release of a water molecule from glycerol. The mechanism of 4-hydroxyphenylacetate decarboxylase has been explored based on continuum electrostatic and hybrid quantum chemical/molecular mechanical calculations. The calculations suggest that the substrate is activated to a radical form by two simultaneous transfers, one of an electron to the thiyl radical and second of a proton to the active site glutamate. This activation mode has not been reported for any known radical enzyme. The mechanism of pyruvate formate-lyase has been investigated based for the first time on the complete enzyme model. The key new finding is that quenching of the formyl radical is performed by one of the active site cysteines and not by coenzyme A, as previously suggested.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Universität Bayreuth

Year

2014

Author dc:creator

• Feliks, Mikolaj

Contributors dc:contributor

• Ullmann, Matthias

Repository record source_url

https://epub.uni-bayreuth.de/id/eprint/39/

OAI identifier oai:identifier

oai:epub.uni-bayreuth.de:39