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

被引：3

作者：

Tundo, Grazia Raffaella ^{[1
]}

Grasso, Giuseppe ^{[2
]}

Persico, Marco ^{[3
]}

Tkachuk, Oleh ^{[3
]}

Bellia, Francesco ^{[4
]}

Bocedi, Alessio ^{[5
]}

Marini, Stefano ^{[1
]}

Parravano, Mariacristina ^{[6
]}

Graziani, Grazia ^{[7
]}

Fattorusso, Caterina ^{[3
]}

Sbardella, Diego ^{[6
]}

机构：

[1] Univ Roma Tor Vergata, Dept Clin Sci & Traslat Med, Via Ric Scientif 1, I-00133 Rome, Italy

[2] Univ Catania, Dept Chem Sci, Viale Andrea Doria 6, I-95125 Catania, Italy

[3] Univ Naples Federico II, Dept Pharm, Via D Montesano 49, I-80131 Naples, Italy

[4] Inst Crystallog, CNR, Via Paolo Gaifami 18, I-95126 Catania, Italy

[5] Univ Roma Tor Vergata, Dept Chem Sci & Technol, Via Ric Scientif 1, I-00133 Rome, Italy

[6] IRCCS Fdn Bietti, Rome, Italy

[7] Univ Roma Tor Vergata, Dept Syst Med, Via Montpellier 1, I-00133 Rome, Italy

来源：

BIOMOLECULES | 2023年 / 13卷 / 10期

关键词：

insulin-degrading enzyme; Alzheimer's disease; diabetes; proteasome; insulin; allostery; AMYLOID BETA-PROTEIN; ALZHEIMERS-DISEASE; DEGRADATION-PRODUCTS; EXTRACELLULAR LEVELS; HEPATOMA-CELLS; SUBSTRATE; PEPTIDE; EXPRESSION; BINDING; TARGET;

D O I：

10.3390/biom13101492

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The insulin-degrading enzyme (IDE) is a Zn2+ peptidase originally discovered as the main enzyme involved in the degradation of insulin and other amyloidogenic peptides, such as the beta-amyloid (A beta) 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.

引用

页数：28

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