Identifizierung von Substratbindestellen in der γ-Sekretase

The lack of detailed information on the interactions between substrates and enzymes is a major gap in understanding the mechanisms of many proteases. Using the Alzheimer’s disease protease γ-secretase as an example, we show how a previously developed versatile chemical biology approach allows to systematically identify molecular interactions with the enzyme at the amino acid level of the substrate. Furthermore, this approach provides additional mechanistic insights that could also aid in the development of advanced drugs against this key protease.