My primary interest is in the dynamics of molecular catalysis, particularly
involving novel co-factors and metal ions. The principle tool of my research
is macromolecular X-ray crystallography, in combination with spectroscopic
techniques both in the crystal and solution, kinetics and mutagenesis. My most
recent approach has been to freeze trap catalytic intermediates in the crystal,
both anaerobically and aerobically, leading to "snapshots" along the reaction
pathway. These are then assembled into a "movie of catalysis" at the molecular
level. A demonstration of the power of this approach for copper-containing amine
oxidases has been published in the journal Science (Wilmot et al., 1999).
The photo on the previous page shows me freeze trapping one of the
catalytic intermediates detailed
in the Science paper. Other enzymes I work with include methylamine dehydrogenase
(containing a novel organic co-factor), and the binuclear copper protein tyrosinase
(the first enzyme in melanin production, the substance that protects our skin from
the harmful rays of the sun). I also work with the iron-containing cytochromes
(involved in energy conversion in metabolism).
My lab also works on metalloproteins implicated in disease states, such as
Alzheimers and Williams Syndrome.
