Identification of inhibitors of the transmembrane protease FlaK of Methanococcus maripaludis.

ABSTRACT: GxGD-type intramembrane cleaving proteases (I-CLiPs) form a family of proteolytic enzymes that feature an aspartate-based catalytic mechanism. Yet, they structurally and functionally largely differ from the classical pepsin-like aspartic proteases. Among them are the archaeal enzyme FlaK, processing its substrate FlaB2 during the formation of flagella and γ-secretase, which is centrally involved in the etiology of the neurodegenerative Alzheimer's disease. We developed an optimized activity assay for FlaK and based on screening of a small in-house library and chemical synthesis, we identified compound 9 as the first inhibitor of this enzyme. Our results show that this intramembrane protease differs from classical pepsin-like aspartic proteases and give insights into the substrate recogniti

SUBMITTER: Coburger I 

PROVIDER: S-EPMC4985597 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature