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多功能蛋白:与人类疾病的关联及现有药物的作用靶点。

Multifunctional Proteins: Involvement in Human Diseases and Targets of Current Drugs.

机构信息

Departament de Bioquímica i Biologia Molecular and Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Barcelona, Spain.

Laboratorio de Inmunología, Universidad de la República Regional Norte-Salto, Rivera 1350, 50000, Salto, Uruguay.

出版信息

Protein J. 2018 Oct;37(5):444-453. doi: 10.1007/s10930-018-9790-x.

Abstract

Multifunctionality or multitasking is the capability of some proteins to execute two or more biochemical functions. The objective of this work is to explore the relationship between multifunctional proteins, human diseases and drug targeting. The analysis of the proportion of multitasking proteins from the MultitaskProtDB-II database shows that 78% of the proteins analyzed are involved in human diseases. This percentage is much higher than the 17.9% found in human proteins in general. A similar analysis using drug target databases shows that 48% of these analyzed human multitasking proteins are targets of current drugs, while only 9.8% of the human proteins present in UniProt are specified as drug targets. In almost 50% of these proteins, both the canonical and moonlighting functions are related to the molecular basis of the disease. A procedure to identify multifunctional proteins from disease databases and a method to structurally map the canonical and moonlighting functions of the protein have also been proposed here. Both of the previous percentages suggest that multitasking is not a rare phenomenon in proteins causing human diseases, and that their detailed study might explain some collateral drug effects.

摘要

多功能性或多任务处理是某些蛋白质执行两个或更多生化功能的能力。本工作的目的是探索多功能蛋白质、人类疾病和药物靶标之间的关系。从 MultitaskProtDB-II 数据库分析多功能蛋白的比例表明,分析的蛋白质中有 78%涉及人类疾病。这一百分比远高于一般人类蛋白中发现的 17.9%。使用药物靶标数据库进行类似的分析表明,在所分析的人类多功能蛋白中,有 48%是当前药物的靶标,而 UniProt 中存在的人类蛋白中只有 9.8%被指定为药物靶标。在这些蛋白质中,几乎有 50%的蛋白质,其规范功能和月光族功能都与疾病的分子基础有关。本文还提出了一种从疾病数据库中识别多功能蛋白的方法,以及一种对蛋白的规范功能和月光族功能进行结构映射的方法。这两个之前的百分比表明,多任务处理在导致人类疾病的蛋白质中并不是罕见现象,对其进行详细研究可能有助于解释一些附带的药物作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55ab/6132618/68a71577927f/10930_2018_9790_Fig1_HTML.jpg

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