The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design-Reference-Cited by-同舟云学术

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

Published:2023-10-07 Issue:10 Volume:13 Page:1492
ISSN:2218-273X
Container-title:Biomolecules
language:en
Short-container-title:Biomolecules

Author:

Tundo Grazia Raffaella¹,Grasso Giuseppe²^ORCID,Persico Marco³^ORCID,Tkachuk Oleh³,Bellia Francesco⁴^ORCID,Bocedi Alessio⁵,Marini Stefano¹,Parravano Mariacristina⁶,Graziani Grazia⁷^ORCID,Fattorusso Caterina³^ORCID,Sbardella Diego⁶

Affiliation:

1. Department of Clinical Science and Traslational Medicine, University of Rome Tor Vergata, Via Della Ricerca Scientifica 1, 00133 Rome, Italy

2. Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy

3. Department of Pharmacy, University of Naples “Federico II”, Via D. Montesano 49, 80131 Napoli, Italy

4. Institute of Crystallography, CNR, Via Paolo Gaifami 18, 95126 Catania, Italy

5. Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy

6. IRCCS—Fondazione Bietti, Rome, Italy

7. Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy

Abstract

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 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.

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry

Link

https://www.mdpi.com/2218-273X/13/10/1492/pdf

Reference169 articles.

1. Human Matrix Metalloproteinases: An Ubiquitarian Class of Enzymes Involved in Several Pathological Processes;Sbardella;Mol. Asp. Med.,2012

2. Multiple Functions of Insulin-Degrading Enzyme: A Metabolic Crosslight?;Tundo;Crit. Rev. Biochem. Mol. Biol.,2017

3. Purification of Insulin-Specific Protease by Affinity Chromatography;Duckworth;Proc. Natl. Acad. Sci. USA,1972

4. Insulin Degradation: Progress and Potential;Duckworth;Endocr. Rev.,1998

5. Human Insulin-Degrading Enzyme Shares Structural and Functional Homologies with E. coli Protease III;Affholter;Science,1988