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一种克服与寻找特定酶靶点以开发抗……药物相关挑战的计算方法

A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs Against .

作者信息

Catharina Larissa, Lima Carlyle Ribeiro, Franca Alexander, Guimarães Ana Carolina Ramos, Alves-Ferreira Marcelo, Tuffery Pierre, Derreumaux Philippe, Carels Nicolas

机构信息

Laboratório de Modelagem de Sistemas Biológicos, Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas (INCT-IDPN), Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil.

Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique (UPR 9080), Centre National de la Recherche Scientifique (CNRS), Université Paris 7, Paris, France.

出版信息

Bioinform Biol Insights. 2017 Jun 12;11:1177932217712471. doi: 10.1177/1177932217712471. eCollection 2017.

DOI:10.1177/1177932217712471
PMID:28638238
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5470852/
Abstract

We present an approach for detecting enzymes that are specific of compared with and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific for compared with , only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific of and 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with . Among the 40 strictly specific enzymes, we identified sterol 24-C-methyltransferase, pyruvate phosphate dikinase, trypanothione synthetase, and RNA-editing ligase as 4 essential enzymes for that may serve as targets for drug development.

摘要

我们提出了一种检测与[具体物质]相比具有特异性的酶的方法，并提供了可能有助于药物研发研究的靶点。该方法基于通过相似性搜索和马尔可夫建模进行序列同源性比较的传统技术；它整合了酶功能、蛋白质二级和三级结构、蛋白质结构域架构以及代谢环境的表征。在由AnEnPi（类似酶管道）分类为与[具体物质]相比具有特异性的42种酶活性所代表的67种酶中，只有40种（23个酶委员会[EC]编号）实际上可被视为严格特异性针对[具体物质]的，27种酶（19个EC编号）因与[具体物质]存在模糊的同源性或类似性而被排除。在这40种严格特异性酶中，我们确定了固醇24 - C - 甲基转移酶、丙酮酸磷酸二激酶、锥虫硫醇合成酶和RNA编辑连接酶为[具体物质]的4种关键酶，它们可能作为药物研发的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6520/5470852/55e53c6f1e98/10.1177_1177932217712471-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6520/5470852/b9bfdebb6e8c/10.1177_1177932217712471-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6520/5470852/3ff7b5ce72a8/10.1177_1177932217712471-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6520/5470852/6a08685a8430/10.1177_1177932217712471-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6520/5470852/6725a63a6896/10.1177_1177932217712471-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6520/5470852/55e53c6f1e98/10.1177_1177932217712471-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6520/5470852/b9bfdebb6e8c/10.1177_1177932217712471-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6520/5470852/3ff7b5ce72a8/10.1177_1177932217712471-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6520/5470852/6a08685a8430/10.1177_1177932217712471-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6520/5470852/6725a63a6896/10.1177_1177932217712471-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6520/5470852/55e53c6f1e98/10.1177_1177932217712471-fig5.jpg

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本文引用的文献

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J Transl Int Med. 2015 Apr-Jun;3(2):43-50. doi: 10.1515/jtim-2015-0002. Epub 2015 Jun 30.
2
In silico structural characterization of protein targets for drug development against Trypanosoma cruzi.用于开发抗克氏锥虫药物的蛋白质靶点的计算机结构表征
J Mol Model. 2016 Oct;22(10):244. doi: 10.1007/s00894-016-3115-9. Epub 2016 Sep 24.
3
Attenuation and Production of the Amphotericin B-Resistant Leishmania tropica Strain.
抗两性霉素B热带利什曼原虫菌株的减毒与产生
Jundishapur J Microbiol. 2016 May 14;9(6):e32159. doi: 10.5812/jjm.32159. eCollection 2016 Jun.
4
Identification of Novel Chemical Scaffolds Inhibiting Trypanothione Synthetase from Pathogenic Trypanosomatids.鉴定抑制致病锥虫硫醇合成酶的新型化学骨架
PLoS Negl Trop Dis. 2016 Apr 12;10(4):e0004617. doi: 10.1371/journal.pntd.0004617. eCollection 2016 Apr.
5
MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets.MEGA7：适用于更大数据集的分子进化遗传学分析版本7.0
Mol Biol Evol. 2016 Jul;33(7):1870-4. doi: 10.1093/molbev/msw054. Epub 2016 Mar 22.
6
Thiol redox biology of trypanosomatids and potential targets for chemotherapy.锥虫的硫醇氧化还原生物学与化疗潜在靶点
Mol Biochem Parasitol. 2016 Mar-Apr;206(1-2):67-74. doi: 10.1016/j.molbiopara.2015.11.003. Epub 2015 Nov 22.
7
Neglected tropical disease research: rethinking the drug discovery model.被忽视的热带病研究：重新思考药物研发模式。
Future Med Chem. 2015;7(6):693-700. doi: 10.4155/fmc.15.29.
8
Properties of protein drug target classes.蛋白质药物靶点类别的特性。
PLoS One. 2015 Mar 30;10(3):e0117955. doi: 10.1371/journal.pone.0117955. eCollection 2015.
9
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PLoS One. 2015 Mar 19;10(3):e0120844. doi: 10.1371/journal.pone.0120844. eCollection 2015.
10
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PLoS Negl Trop Dis. 2015 Mar 13;9(3):e0003588. doi: 10.1371/journal.pntd.0003588. eCollection 2015 Mar.