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胰岛素降解酶：从结构到别构调节的探索——药物设计的新视角。

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

机构信息

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

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

出版信息

Biomolecules. 2023 Oct 7;13(10):1492. doi: 10.3390/biom13101492.

DOI:10.3390/biom13101492
PMID:37892174
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10604886/
Abstract

The insulin-degrading enzyme (IDE) is a Zn 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.

摘要

胰岛素降解酶（IDE）是一种 Zn 肽酶，最初被发现是参与胰岛素和其他淀粉样肽（如β-淀粉样（Aβ）肽）降解的主要酶。因此，IDE 在治疗糖尿病和阿尔茨海默病（AD）中的作用早已被设想。然而，其在降解淀粉样蛋白中的作用仍未明确界定，最近提出了 IDE 的新型非蛋白水解功能。从结构的角度来看，IDE 呈现出非典型的蛤壳结构，突出了独特的神秘酶学特性。更好地理解结构-功能关系可能有助于解决 IDE 生物学中的一些现有悖论，并且鉴于其多功能活性，可能会导致新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/d05be16653d3/biomolecules-13-01492-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/0e245cac751f/biomolecules-13-01492-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/35ea86f133f0/biomolecules-13-01492-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/9b8bc1e7ed04/biomolecules-13-01492-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/6a72f311595e/biomolecules-13-01492-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/6765c625255b/biomolecules-13-01492-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/7d22f7dadea9/biomolecules-13-01492-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/23b692e4516b/biomolecules-13-01492-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/1f8a522d10a8/biomolecules-13-01492-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/f5b990e6a1bc/biomolecules-13-01492-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/bb39351468ce/biomolecules-13-01492-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/1f84a11dee9d/biomolecules-13-01492-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/d05be16653d3/biomolecules-13-01492-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/0e245cac751f/biomolecules-13-01492-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/35ea86f133f0/biomolecules-13-01492-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/9b8bc1e7ed04/biomolecules-13-01492-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/6a72f311595e/biomolecules-13-01492-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/6765c625255b/biomolecules-13-01492-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/7d22f7dadea9/biomolecules-13-01492-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/23b692e4516b/biomolecules-13-01492-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/1f8a522d10a8/biomolecules-13-01492-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/f5b990e6a1bc/biomolecules-13-01492-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/bb39351468ce/biomolecules-13-01492-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/1f84a11dee9d/biomolecules-13-01492-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a075/10604886/d05be16653d3/biomolecules-13-01492-g011.jpg

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Increased levels of insulin-degrading enzyme in patients with type 2 diabetes mellitus.
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