Altered Hinge Conformations in APP Transmembrane Helix Mutants May Affect Enzyme-Substrate Interactions of γ-Secretase.

Abstract excerpt

Cleavage of substrates by γ-secretase is an inherently slow process where substrate-enzyme affinities cannot be broken down into specific sequence requirements in contrast to soluble proteases. Nevertheless, despite its apparent sequence tolerance single point mutations in amyloid precursor protein can severely affect cleavage efficiencies and change product line preferences. We have determined by NMR...

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