Phd on topic: Catalytic mechanism and substrate specificity of oxim-reductases

Research interest and scientific background: The Gruber group is interested in structure-function relationships of enzymes, focusing on experimental structure determination, structural bioinformatics and molecular modeling. These studies involve enzymes ranging from flavoenzyme and B12-dependent enzymes to proteases and lipases and aim at a deeper understanding of enzymatic mechanisms of enzymes in general as well as at engineering and (re)designing of biocatalysts for specific applications.

Affiliation: The student will work at the Institute of Molecular Biosciences at the University of Graz. This project is directly connected to the doc.funds CataLOX.

Hypothesis and objective: In close collaboration with the groups of Silvia Glück-Harter and Wolfgang Kroutil the project aims to investigate structure-function relationships of flavin dependent oxime reductases. Preliminary studies have indicated that some oximes are reduced presumably via highly reactive intermediates, the details of the enzymatic mechanism and the structural determinants substrate and stereospecificity are still largely unknown. This project aims at rectifying this situation.

Experimental approaches: The student will use a combination of experimental structure determination (by X-ray crystallography) and a range of (structural) bioinformatics and molecular modeling techniques (e.g. docking calculations, molecular dynamics simulations,…) to elucidate the mode of substrate binding and to identify crucial active site residues. These studies will provide suggestions for (more suitable) enzyme variants and will receive feedback from the biocatalytic experiments performed in the collaborating groups.

The student will strongly interact with other research groups of the doc.funds Molecular Metabolism, the doc.funds CataLOX and the Austrian Centre of Industrial Biotechnology (acib).