Research
Many proteins involved in central cellular pathways rely on allosteric interactions in addition to direct interactions to ensure substrate or binding specificity. This specificity is often crucial to the fate of cell, hence elucidating the allosteric mechanism in these interactions is important in understanding various diseases and designing target-specific drugs.
The general goal of the Wang lab is recognizing that supporting actors in biology still play a major role in the story, and trying to learn how they go about doing that.
Specifically the lab is interested in studying SIRT1, an enzyme that affects gene
expression by de-acetylating transcription factors and histones. The activity of
SIRT1 plays a major role in neurodegenerative diseases and the aging process. However
the mechanism of SIRT1’s substrate specificity is not well understood. SIRT1 has a
large, unstructured N-terminus domain that is not directly involved in enzyme catalysis,
but regulates the catalytic activity and substrate specificity. The lab seeks to elucidate
the mechanism of this allosteric effect by studying the interactions between the N-terminus
domain and the enzyme catalytic core. To this end, we carry out biophysical experiments
defining these interactions in combination with enzyme activity assays.
