Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Degradation of Alzheimers Amyloid-beta by a Catalytically Inactive Insulin Degrading Enzyme It is known that insulin-degrading-enzyme (IDE) plays a crucial role in the clearance of Alzheimers amyloid-{beta} (A{beta}). The cysteine-free IDE mutant (cf-E111Q-IDE) is catalytically inactive against insulin, but its effect on A{beta} degradation is unknown that would help in the allosteric modulation of the enzyme activity. Herein, the degradation of A{beta}(1-40) by cf-E111Q-IDE via a non-chaperone mechanism is demonstrated by NMR and LC-MS, and the aggregation of fragmented peptides is characterized using fluorescence and electron microscopy. cf-E111Q-IDE presented a reduced effect on the aggregation kinetics of A{beta}(1-40) when compared with the wild-type IDE. Whereas LC-MS and diffusion ordered NMR spectroscopy revealed the generation of A{beta} fragments by both wild-type and cf-E111Q-IDE. The aggregation propensities and the difference in the morphological phenotype of the full-length A{beta}(1-40) and its fragments are explained using multi-microseconds molecular dynamics simulations. Notably, our results reveal that zinc binding to A{beta}(1-40) inactivates cf-E111Q-IDEs catalytic function, whereas zinc removal restores its function as evidenced from high-speed AFM, electron microscopy, chromatography, and NMR results. These findings emphasize the catalytic role of cf-E111Q-IDE on A{beta} degradation and urge the development of zinc chelators as an alternative therapeutic strategy that switches on/off IDEs function.
27
The categories of this paper are: pathology
23
The categories of this paper are: immunology
16
The categories of this paper are: microbiology
1
The categories of this paper are: bioinformatics
21
The categories of this paper are: toxicology
31
The categories of this paper are: paleontology
7
The categories of this paper are: ecology
5
The categories of this paper are: cell
32
The categories of this paper are: zoology
19
The categories of this paper are: epidemiology
25
The categories of this paper are: bioengineering
30
The categories of this paper are: scientific
11
The categories of this paper are: cognition
22
The categories of this paper are: physiology
20
The categories of this paper are: pharmacology
0
The categories of this paper are: genetics