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D3DistalMutation: a Database to Explore the Effect of Distal Mutations on Enzyme Activity

文献类型：期刊论文

作者Wang, Xiaoyu1,2,3; Zhang, Xinben1,2; Peng, Cheng1,2; Shi, Yulong1,2; Li, Huiyu3; Xu, Zhijian1,2; Zhu, Weiliang1,2
刊名JOURNAL OF CHEMICAL INFORMATION AND MODELING
出版日期2021-05-24
卷号61期号:5页码:2499-2508
ISSN号1549-9596
DOI10.1021/acs.jcim.1c00318
通讯作者Xu, Zhijian(zjxu@simm.ac.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn)
英文摘要Enzyme activity is affected by amino acid mutations, particularly mutations near the active site. Increasing evidence has shown that distal mutations more than 10 A away from the active site may significantly affect enzyme activity. However, it is difficult to study the enzyme regulation mechanism of distal mutations due to the lack of a systematic collection of three-dimensional (3D) structures, highlighting distal mutation site and the corresponding enzyme activity change. Therefore, we constructed a distal mutation database, namely, D3DistalMutation, which relates the distal mutation to enzyme activity. As a result, we observed that approximately 80% of distal mutations could affect enzyme activity and 72.7% of distal mutations would decrease or abolish enzyme activity in D3DistalMutation. Only 6.6% of distal mutations in D3DistalMutation could increase enzyme activity, which have great potential to the industrial field. Among these mutations, the Y to F, S to D, and T to D mutations are most likely to increase enzyme activity, which sheds some light on industrial catalysis. Distal mutations decreasing enzyme activity in the allosteric pocket play an indispensable role in allosteric drug design. In addition, the pockets in the enzyme structures are provided to explore the enzyme regulation mechanism of distal mutations. D3DistalMutation is accessible free of charge at https://www.d3pharma.com/D3DistalMutation/index.php.
WOS关键词CRYSTAL-STRUCTURE ; SITE
资助项目National Natural Science Foundation of China[31870717] ; National Key R&D Program of China[2016YFA0502800] ; National Key R&D Program of China[2016YFA0502301]
WOS研究方向Pharmacology & Pharmacy ; Chemistry ; Computer Science
语种英语
WOS记录号WOS:000656118800035
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/297062]  
专题中国科学院上海药物研究所
通讯作者Xu, Zhijian; Zhu, Weiliang
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
3.Shanghai Univ Elect Power, Coll Math & Phys, Shanghai 200090, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Xiaoyu,Zhang, Xinben,Peng, Cheng,et al. D3DistalMutation: a Database to Explore the Effect of Distal Mutations on Enzyme Activity[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING,2021,61(5):2499-2508.
APA Wang, Xiaoyu.,Zhang, Xinben.,Peng, Cheng.,Shi, Yulong.,Li, Huiyu.,...&Zhu, Weiliang.(2021).D3DistalMutation: a Database to Explore the Effect of Distal Mutations on Enzyme Activity.JOURNAL OF CHEMICAL INFORMATION AND MODELING,61(5),2499-2508.
MLA Wang, Xiaoyu,et al."D3DistalMutation: a Database to Explore the Effect of Distal Mutations on Enzyme Activity".JOURNAL OF CHEMICAL INFORMATION AND MODELING 61.5(2021):2499-2508.

入库方式： OAI收割

来源：上海药物研究所

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