Bioinformatic Study of γ-Secretase and its Substrates
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چکیده
Bioinformatic Study of γ-Secretase and its Substrates
منابع مشابه
Analysis of domain interactions among gamma-secretase substrates
The γ-secretase plays a key role in the Amyloid hypothesis of the cause of Alzheimer’s disease. The integral membrane protein cleaves single-pass transmembrane proteins at residues within the transmembrane domain. In this work, we proposed a new model to analyze the relationships among the identified substrates of γ-secretase at the domain level. Firstly the sequence features in domains of γ-se...
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γ-Secretase generates the peptides of Alzheimer's disease, Aβ(40) and Aβ(42), by cleaving the amyloid precursor protein within its transmembrane domain. γ-Secretase also cleaves numerous other substrates, raising concerns about γ-secretase inhibitor off-target effects. Another important class of drugs, γ-secretase modulators, alter the cleavage site of γ-secretase on amyloid precursor protein, ...
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γ-Secretase is a four subunit, 19-pass transmembrane enzyme that cleaves amyloid precursor protein (APP), catalyzing the formation of amyloid beta (Aβ) peptides that form amyloid plaques, which contribute to Alzheimer's disease (AD) pathogenesis. γ-Secretase also cleaves Notch, among many other type I transmembrane substrates. Despite its seemingly promiscuous enzymatic capacity, γ-secretase ac...
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Alzheimer’s disease is characterized by protein deposits of amyloid-β as plaques in the brain (1). The suite of enzymes that produce amyloid-β by cutting it out of the amyloid-β precursor protein (APP) have long been considered to be prime targets for therapeutic intervention. Converting this promise into reality, however, continues to be stalled by a series of obstacles, including an inaccurat...
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Understanding the substrate recognition mechanism of γ-secretase is a key step for establishing substrate-specific inhibition of amyloid β-protein (Aβ) production. However, it is widely believed that γ-secretase is a promiscuous protease and that its substrate-specific inhibition is elusive. Here we show that γ-secretase distinguishes the ectodomain length of substrates and preferentially captu...
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