Walczewska-Szewc, Katarzyna
Katarzyna Walczewska-Szewc is an assistant professor in the Theoretical Biophysics group, Nicolaus Copernicus University in Toruń, Poland. In her research she uses a number of computer-aided methods to model biomolecular interactions and to reveal the structural mechanisms of action of medically important proteins. She obtained her PhD degree in biology and physics jointly from the Australian National University and University of Gdansk, Poland. Katarzyna’s PhD project involved the development and use of numerical and simulation methods to design and interpret Förster resonance energy transfer (FRET) experiments in physics and biology
Abstract:
The changes in prolyl oligopeptidase structure upon inhibition modify its ability to decrease alpha-synuclein aggregation
Topic:
The formation of extended misfolded protein aggregates is one of the main reasons for neuronal malfunction and, eventually, brain damage in many neurodegenerative diseases. In Parkinson’s disease alpha-synucleins are implicated in the accumulation of the aggregates. The origin of such aggregation is not yet known, however, there is a compelling evidence that it can be reduced by inhibition of prolyl oligopeptidase (PREP). This effect cannot be simply related to the inhibition of the catalytic function of the enzyme, as not all PREP inhibitors stop the alpha-synuclein aggregation. Finding differences in the dynamics of the enzyme inhibited with diverse compounds would allow us to pinpoint the regions of the protein involved in the interaction between PREP and alpha-synuclein. Here, we study the action of three PREP inhibitors, each of which affects alphasynuclein aggregation to different extent. Using molecular dynamics modelling, we determine molecular mechanisms underlying the PREP inhibition and identify structural differences in each inhibitor-PREP system. We suggest that even subtle differences in the dynamics of the enzyme affect its interactions with alpha-synucleins. Thus, identification of these regions may be crucial in preventing formation of alpha-synuclein aggregates. Acknowledgement: The computational results were obtained using the facilities of the Interdisciplinary Centre for Modern Technologies, NCU, Poland
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