Structural Biochemistry - Doreen Dobritzsch

Structural and functional characterization of the three enzymes of the reductive pyrimidine degradation pathway.

Our research aims at the elucidation of protein structures and functions in order to further our understanding of the relationship between the two. Questions we want to answer are e.g. which specific structural features enable a particular function and how structural alterations affect it. We focus on medically or biotechnologically relevant proteins, with the main focus being on structural enzymology of pathways for uracil and thymine degradation. Major collaborative projects concern molecular recognition in immune complexes associated with development and progression of rheumatoid arthritis, and structural determinants that govern substrate specificity, regio- and stereoselectivity in laboratory-evolved enzyme variants of interest for biocatalysis applications. We use X-ray crystallography together with other biochemical and biophysical methods to explore structures, functions and interactions of these proteins. 

Curious to know more? Our popular science presentation below provides an easily accessible introduction to our research.

PI: Doreen Dobritzsch-Lohkamp

Our research projects

  • Pyrimidine metabolism
  • Molecular recognition in RA autoimmune complexes
  • Additional projects

Popular Scientific Presentation

Structure and function of a protein are intimately linked. For example, the structure of a catalytic protein (enzyme) that converts one chemical compound into another needs to contain a binding site to which (only) this chemical compound can dock, and in which protein residues that help with the chemical conversion are appropriately placed. If the structure of a protein is changed, e.g. as a result of mutations in the gene that encodes its amino acid sequence, the function of the protein is also affected. This often causes disease, which can be treated more effectively if one knows what changes occurred at molecular level. Knowledge of structure function relationships is also important for many biotechnological applications such as design of more active or more stable enzymes for the food industry.

The aim of our research is to reveal the structure and function of proteins that are of medical or biotechnological importance. For example, we want to know how the enzymes that break down uracil and thymine, building blocks of DNA and RNA, look like and function, and why molecules of our immune system by mistake recognize and attack our own joint collagen as foreign, which leads to development and progression of rheumatoid arthritis. We use X-ray crystallography combined with other biochemical and biophysical methods to study the structure, function and interactions of these proteins.