Conveners
Biocrystallography: Enzymes
- Wulf Blankenfeldt (DGK)
The DYW domain, an enzyme for plant RNA editing: Pentatricopeptide repeat (PPR) proteins with a C-terminal DYW domain are responsible for C to U RNA editing in plants. We show that the DYW domain harbors the cytidine deaminase activity by functional data in vitro and structural similarity to distinctly related known cytidine deaminases. A DYW-specific domain regulates the active site...
PlaB is a secreted phospholipase of Legionella pneumophila, the causative agent of Legionnaires' Disease. It is an unusual enzyme that looses activity at higher concentrations due to tetramer formation.
Here, we show the crystal structure of PlaB in its inactive tetrameric form. We find that the tetramer is stabilized by NAD(H), a central metabolite only found within the cell. This...
The innate immune sensor 2’-5’-oligoadenylate synthetase (OAS) is among the most promising targets for the development of new antivirals. Here we report the results of kinetic crystallography, mutagenesis, and computational chemistry studies of the OAS1 product release mechanism. These investigations provide new insights into the rate-limiting steps of innate immune signaling, which can help...
I will present crystallographic snapshots of the human enzyme orotidine-5-monophosphate decarboxylase in complex with the genuine substrate, substrate analogs, transition state analogs and product - all at true atomic resolution. These snapshots of catalysis defy the proposed mechanism of ground-state destabilization by revealing that the substrate carboxylate is protonated and forms a...
