PhD ceremony: Mr. W.T. Ismaya, 14.45 uur, Doopsgezinde Kerk, Oude Boteringestraat 33, Groningen
Dissertation: Crystal structure of Agaricus bisporus tyrosinase
Promotor(s): prof. B.W. Dijkstra, prof. H.J. Wichers
Faculty: Mathematics and Natural Sciences
A tyrosinase from the mushroom Agaricus bisporus has successfully been crystallized by Wangsa Ismaya and its structure was elucidated by means of X-ray crystallography.
The structure of this copper-containing enzyme shows a tetramer of two heavy (H) and two light (L) subunits, which is the species occurring physiologically. The H subunit appeared to be the gene product of ppo3 and has the typical fold of type 3 binuclear copper proteins, although with several extensions of the peptide chain. The L subunit originates from orf239342. Its structure resembles that of proteins with agglutinating activity, but the carbohydrate binding residues are not conserved; therefore its function is not yet clear. The tyrosinase structure shows how calcium ions stabilize the tetramer. A thioether bond, which occurs between the Cu-A coordinating His85 and the adjacent Cys83, is present in the active site. This thioether bond restricts the rotational freedom of the His85 side chain. A structure of PPO3 with bound tropolone shows that this inhibitor forms a pre-Michaelis complex with the enzyme. It occupies a similar position to that of phenylthiourea in the structure of catechol oxidase, a tyrosinase homolog. Further details of the reaction mechanism remain unclear in the absence of data on the oxygen-bound (oxy-state) of the enzyme. Nevertheless, the presence of a thioether bond suggests that the current catalytic mechanism, which requires His85 to be flexible, should be updated. In addition, the structure provides now a solid base for the biochemical characterization of the L subunit.
The ENLIGHT consortium of nine European universities, including the University of Groningen, was selected within the framework of the second call for ‘European Universities’, the European Commission's pilot program for new multilateral networks....
Aan het einde van de zomer komen er naast veel Nederlandse studenten ook internationale studenten naar Groningen om voor kortere of langere tijd te studeren aan de Hanzehogeschool Groningen (HG) of de Rijksuniversiteit Groningen (RUG). Vanwege de...
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