Isolation and Characterization of Reactive Heme -Oxygen Intermediates in Cytochrome P450 Catalysis

The P450 monooxygenases, and specifically the intermediate species formed within the course of their reaction cycle, are formidable oxidants, capable of a diverse range of chemical reactions. As the cryoradiolytic methodologies prove a convenient tool for the isolation and stabilization of heme-oxygen intermediates, a range of substrate probes has been coupled to these studies in order to assess their role in known P450 reactions. This provides a template not only for the assorted reactivity of the P450 superfamily, but the utilization of related intermediates in other metalloenzyme systems. In order to assess the commonality of these intermediates, the ferric-peroxo species have also been generated in a number of other heme enzyme systems in order to assess the role of proximal ligand and distal pocket in the proton mediated functionalization of these reactive intermediates, and thus, to compare these to the reaction mechanism associated with the P450 monoxygenases.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics and Computational Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Makris, Thomas Michael

Contributors dc:contributor

• Sligar, Stephen G.

• Chemistry, Biochemistry

Language dc:language

eng

Identifier

(MiAaPQ)AAI3130976

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/85436