Structural Enzymology: A Quantitative Approach

Project description

Strategic research project of the University of Oulu
Focus institute: Biocenter Oulu
Faculty: Faculty of Biochemistry and Molecular Medicine (FBMM)

The ongoing structural enzymological studies of collagen prolyl 4-hydroxylase (C-P4H, α2β2, 240kD) and trifunctional enzyme (TFE, α2β2, 240kD) remain challenging. The TFEs are acyl-CoA dependent enzymes, catalysing three steps of the β-oxidation pathway. Other CoA, thioester dependent enzymes that are being studied concern multifunctional enzyme, type-1 (MFE1) and the monofunctional enzymes enoyl-CoA-hydratase, enoyl-CoA-isomerase and thiolase. In each of these projects we study all aspects of the reaction mechanisms ranging from processivity (C-P4H), substrate channeling (TFE, MFE1) to the role of hydrogen bond networks in the active sites, using a multidisciplinary approach including biocomputing, chemistry and structural enzymology. The insight from these enzyme mechanistic studies is highly relevant for drug discovery applications, as well as for the development of non-natural enzymes providing more sustainable synthesis methods of high value compounds.