Bertram Dillon Steele Public Lecture

Event Details

Date:

Monday, 22 June 2015

Time:

3:15 pm - 4:15 pm

Room:

360

UQ Location:

Physiology Lecture Theatres (St Lucia)

Event category(s):

Full Description:: 2015 Guest Speaker:Professor Mike Green

Capture and characterisation of reactive intermediates in P450 catalysis: Insights into biological C-H bond activation Cytochromes P450 play critical roles in hormone synthesis and drug metabolism. Since the discovery of P450s over four decades ago, chemists have been enamoured with their ability to selectively functionalise a wide range of organic compounds.

The enzyme’s ability to perform demanding oxidations of inert hydrocarbons without damage to its own relatively fragile protein superstructure has been an enigmatic aspect of P450 chemistry. Professor Green’s research has examined reactive intermediates in P450 catalysis to solve this mystery.

It has been proposed that remarkably high pKa of the important ferryl (iron(IV)oxo) intermediate in P450 oxidations is key to this enzyme’s selectivity. Prof Green provided experimental evidence for this proposal by employing Mössbauer and UV/Visible spectroscopies (in conjunction with X-ray absorption measurements) to determine a ferryl pKa of 11.9 in CYP158. Arguments based on Marcus theory indicate that the resultant change in ferryl redox potential dramatically reduces the rate constant for oxidations of the protein superstructure, making these processes noncompetitive with substrate C-H bond activation.