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利用计算机辅助药物设计鉴定高尔基 α-甘露糖苷酶 II 的一个潜在别构位点。

Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.

机构信息

Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany.

Department of Biomedicine, University of Bergen, Bergen, Norway.

出版信息

PLoS One. 2019 May 8;14(5):e0216132. doi: 10.1371/journal.pone.0216132. eCollection 2019.

DOI:10.1371/journal.pone.0216132
PMID:31067280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6505943/
Abstract

Golgi α-mannosidase II (GMII) is a glycoside hydrolase playing a crucial role in the N-glycosylation pathway. In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis. GMII therefore is a possible molecular target for anticancer agents. Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.

摘要

高尔基 α-甘露糖苷酶 II（GMII）是糖苷水解酶，在 N-糖基化途径中发挥着关键作用。在各种肿瘤细胞系中，细胞表面 N-连接糖的分布发生改变，并与肿瘤转移的进展相关。因此，GMII 是抗癌药物的一个潜在的分子靶点。在这里，我们描述了使用计算机辅助药物设计方法鉴定非竞争性 GMII 抑制剂的过程，包括确定可能的别构结合位点、药效团搜索和虚拟筛选。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/4c8901a35264/pone.0216132.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/71020b9a7133/pone.0216132.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/4d82803fd182/pone.0216132.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/02ea05a65857/pone.0216132.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/afb9988cdbdf/pone.0216132.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/4f9391661fdc/pone.0216132.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/8b2255bf52ea/pone.0216132.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/9d6e5456ad20/pone.0216132.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/64cd1878d167/pone.0216132.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/ec14b7799951/pone.0216132.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/4c8901a35264/pone.0216132.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/71020b9a7133/pone.0216132.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/4d82803fd182/pone.0216132.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/02ea05a65857/pone.0216132.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/afb9988cdbdf/pone.0216132.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/4f9391661fdc/pone.0216132.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/8b2255bf52ea/pone.0216132.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/9d6e5456ad20/pone.0216132.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/64cd1878d167/pone.0216132.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/ec14b7799951/pone.0216132.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a27/6505943/4c8901a35264/pone.0216132.g010.jpg

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1
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ACS Cent Sci. 2017 Jul 26;3(7):784-793. doi: 10.1021/acscentsci.7b00214. Epub 2017 Jul 13.
3
UniProt: the universal protein knowledgebase.通用蛋白质知识库：UniProt
硒化硫破坏 PLAGL2/C-MET/STAT3 诱导的肝癌细胞对线粒体凋亡的耐药性。
Clin Transl Med. 2021 Sep;11(9):e536. doi: 10.1002/ctm2.536.
4
Unlocking COVID therapeutic targets: A structure-based rationale against SARS-CoV-2, SARS-CoV and MERS-CoV Spike.解锁新冠病毒治疗靶点：基于结构的抗严重急性呼吸综合征冠状病毒2、严重急性呼吸综合征冠状病毒和中东呼吸综合征冠状病毒刺突蛋白的理论依据。
Comput Struct Biotechnol J. 2020 Jul 31;18:2117-2131. doi: 10.1016/j.csbj.2020.07.017. eCollection 2020.
Nucleic Acids Res. 2017 Jan 4;45(D1):D158-D169. doi: 10.1093/nar/gkw1099. Epub 2016 Nov 29.
4
The role of ligand efficiency metrics in drug discovery.配体效率指标在药物发现中的作用。
Nat Rev Drug Discov. 2014 Feb;13(2):105-21. doi: 10.1038/nrd4163.
5
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Glycobiology. 2014 Mar;24(3):252-61. doi: 10.1093/glycob/cwt106. Epub 2013 Dec 1.
6
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9
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J Chem Inf Model. 2012 Feb 27;52(2):360-72. doi: 10.1021/ci200454v. Epub 2012 Jan 5.