Mechanistic study of human aspartate/asparagine-b-hydroxylase

Enzymes are biological catalysts which enable efficient and specific chemical reactions and are thus essential for life. Enzymes can be classified according to their three-dimensional structure, for example the 2-oxogluatarate (2OG)-dependent oxygenases are structurally similar. These 2OG oxygenases catalyse different reactions but all utilize O2 and 2OG as cosubstrates. In contrast to most other reported human 2OG hydroxylases, aspartate/asparagine-b-hydroxylase (AspH), bears an unusual catalytic centre as its central metal ion is only complexed by two ligands rather than the typical three ligands. The reason for this structural particularity is currently unknown. As inactivating mutations in AspH have been linked to human disease and AspH is sometimes observed on the surface of cancer cells, correlating its structure to biologic function is desirable. This project will employ state-of-the-art time-resolved X-ray spectroscopy methods to investigate the structure of AspH with the aim to unravel its molecular mechanism. In conjunction with biological assays, this work will enable future work in the development of small molecules which could be used as medicines.