Membrane Proteins

Probing the activity of two proteases

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Science  21 Aug 2015:
Vol. 349, Issue 6250, pp. 839-840
DOI: 10.1126/science.349.6250.839-b

Presinilin (PS), the transmembrane catalytic subunit of the enzyme γ-secretase, is a drug target of high interest. This is because it cleaves both amyloid precursor protein, which is implicated in Alzheimer's disease, and Notch, a protein involved in several cancers. How potential therapeutics may affect related proteins, such as signal peptide peptidase (SPP), an enzyme that has an active site similar to that of PS, is unclear. To investigate this, Gertsik et al. designed photolabeled molecular probes that targeted different parts of the catalytic subpockets of the enzymes. Comparing the labeling profiles of the probes revealed important similarities and differences between the two enzymes. Scientists should take into account such cross-talk as drug development proceeds.

ACS Chem. Biol. 10.1021/acschembio.5b00321 (2015).

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