DAD – Dihydroxyacetophenone Dioxygenase

Why Study DAD?

Protein crystal of 2,4-dihydroxyacetophenone dioxygenaseDetailed knowledge of this protein’s atomic structure may allow us to determine how it functions and once that is known, it is possible to intelligently manipulate the structure to make it breakdown chemicals that it does not catabolise naturally. Environmental issues dominate today’s news, particularly pollution and the resultant change in climate because we are constantly producing more waste and emissions than can safely and effectively be dealt with.  Aromatic hydrocarbons, formed by the incomplete burning of fossil fuels as well as those found in other sources such as plastics and pesticides, are especially damaging to the environment. This is because they are not naturally degraded and therefore persist within the biosphere for many, many years. Bioremediation is a relatively new way of thinking about waste disposal, potentially using microorganisms that have naturally evolved to catabolise aromatic compounds present in the environment, to utilise them as a carbon source.  By learning more about the enzymes involved in this catabolic pathway, like dioxygenases, it may be possible to genetically modify them to degrade pollutant hydrocarbons such as those from petroleum, significantly reducing their negative impact on the environment.

What Does DAD Do?

This dioxygenase is of interest because it catalyses hydrocarbons in a unique manner and its sequence shows little similarity to any other protein. By determining its three-dimensional structure and analysing complexes of this enzyme and mutants, an improved understanding of its catalytic mechanism can be gained. It may then be possible to mutate the protein at specific residues or regions in order to alter the compounds it is able to catabolise to something like aromatic hydrocarbons.

Crystallization and preliminary X-ray characterization of the 2,4-dihydroxyacetophenone dioxygenase from Alcaligenes sp. 4HAP
Acta Cryst. 2014 May; F70: 828-8302-826dt>

G. Beaven, Bowyer A, P. Erskine, S. P. Wood, A. McCoy, L. Coates, R. Keegan, A. Lebedev, D. J. Hopper, M. A. Kaderbhai and J. B. Cooper