The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.

Autor: Tundo GR; Department of Clinical Science and Traslational Medicine, University of Rome Tor Vergata, Via Della Ricerca Scientifica 1, 00133 Rome, Italy., Grasso G; Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy., Persico M; Department of Pharmacy, University of Naples 'Federico II', Via D. Montesano 49, 80131 Napoli, Italy., Tkachuk O; Department of Pharmacy, University of Naples 'Federico II', Via D. Montesano 49, 80131 Napoli, Italy., Bellia F; Institute of Crystallography, CNR, Via Paolo Gaifami 18, 95126 Catania, Italy., Bocedi A; Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy., Marini S; Department of Clinical Science and Traslational Medicine, University of Rome Tor Vergata, Via Della Ricerca Scientifica 1, 00133 Rome, Italy., Parravano M; IRCCS-Fondazione Bietti, Rome, Italy., Graziani G; Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy., Fattorusso C; Department of Pharmacy, University of Naples 'Federico II', Via D. Montesano 49, 80131 Napoli, Italy., Sbardella D; IRCCS-Fondazione Bietti, Rome, Italy.
Jazyk: angličtina
Zdroj: Biomolecules [Biomolecules] 2023 Oct 07; Vol. 13 (10). Date of Electronic Publication: 2023 Oct 07.
DOI: 10.3390/biom13101492
Abstrakt: The insulin-degrading enzyme (IDE) is a Zn 2+ peptidase originally discovered as the main enzyme involved in the degradation of insulin and other amyloidogenic peptides, such as the β-amyloid (Aβ) peptide. Therefore, a role for the IDE in the cure of diabetes and Alzheimer's disease (AD) has been long envisaged. Anyway, its role in degrading amyloidogenic proteins remains not clearly defined and, more recently, novel non-proteolytic functions of the IDE have been proposed. From a structural point of view, the IDE presents an atypical clamshell structure, underscoring unique enigmatic enzymological properties. A better understanding of the structure-function relationship may contribute to solving some existing paradoxes of IDE biology and, in light of its multifunctional activity, might lead to novel therapeutic approaches.
Databáze: MEDLINE
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