Identification of serine 119 as an effective inhibitor binding site of m. tuberculosis ubiquitin-like protein ligase pafa using purified proteins and m. smegmatis
文献类型：期刊论文
| 作者 | Jiang, He-Wei1; Czajkowsky, Daniel M.2,3; Wang, Tao4,5; Wang, Xu-De6; Wang, Jia-bin1; Zhang, Hai-Nan1; Liu, Cheng-Xi1; Wu, Fan-Lin1; He, Xiang1; Xu, Zhao-Wei1 |
| 刊名 | Ebiomedicine
 |
| 出版日期 | 2018-04-01 |
| 卷号 | 30页码:225-236 |
| 关键词 | M. tuberculosis Pupylation Pafa 4-(2-aminoethyl) benzenesulfonyl fluoride |
| ISSN号 | 2352-3964 |
| DOI | 10.1016/j.ebiom.2018.03.025 |
| 通讯作者 | Tao, sheng-ce(taosc@sjtu.edu.cn) |
| 英文摘要 | Owing to the spread of multidrug resistance (mdr) and extensive drug resistance (xdr), there is a pressing need to identify potential targets for the development of more-effective anti-m. tuberculosis (mtb) drugs. pafa, as the sole prokaryotic ubiquitin-like protein ligase in the pup-proteasome system (pps) of mtb, is an attractive drug target. here, we show that the activity of purified mtb pafa is significantly inhibited upon the association of aebsf (4-(2-aminoethyl) benzenesulfonyl fluoride) to pafa residue serine 119 (s119). mutation of s119 to amino acids that resemble aebsf has similar inhibitory effects on the activity of purified mtb pafa. structural analysis reveals that although s119 is distant from the pafa catalytic site, it is located at a critical position in the groove where pafa binds the c-terminal region of pup. phenotypic studies demonstrate that s119 plays critical roles in the function of mtb pafa when tested in m. smegmatis. our study suggests that targeting s119 is a promising direction for developing an inhibitor of m. tuberculosis pafa. (c) 2018 the author(s). published by elsevier b.v. |
| WOS关键词 | PROTEASOMAL ATPASE HOMOLOG ; GENERAL FORCE-FIELD ; MYCOBACTERIUM-TUBERCULOSIS ; STRUCTURAL INSIGHTS ; MOLECULAR-DYNAMICS ; NITRIC-OXIDE ; PUP LIGASE ; IN-VIVO ; PUPYLATION ; DRUG |
| WOS研究方向 | General & Internal Medicine ; Research & Experimental Medicine |
| WOS类目 | Medicine, General & Internal ; Medicine, Research & Experimental |
| 语种 | 英语 |
| WOS记录号 | WOS:000430303000028 |
| 出版者 | ELSEVIER SCIENCE BV |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373317 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Tao, Sheng-Ce |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Minist Educ, Key Lab Syst Biomed, Shanghai Ctr Syst Biomed, Shanghai 200240, Peoples R China 2.Shanghai Jiao Tong Univ, BioID Ctr, Sch Biomed Engn, Shanghai 200240, Peoples R China 3.Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200240, Peoples R China 4.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518055, Peoples R China 5.Shenzhen Ctr Dis Control & Prevent, SZCDC SUSTech Joint Key Lab Trop Dis, Shenzhen 518055, Peoples R China 6.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China 7.Chinese Acad Sci, Inst Biophys, Natl Key Lab Biomacromol, Key Lab Noncoding RNA, Beijing 100101, Peoples R China 8.Chinese Acad Sci, Inst Biophys, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China 9.TB Healthcare Biotechnol Co Ltd, Foshan 528000, Guangdong, Peoples R China 10.Foshan Univ, Sch Stomatol & Med, Foshan 528000, Guangdong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, He-Wei,Czajkowsky, Daniel M.,Wang, Tao,et al. Identification of serine 119 as an effective inhibitor binding site of m. tuberculosis ubiquitin-like protein ligase pafa using purified proteins and m. smegmatis[J]. Ebiomedicine,2018,30:225-236. |
| APA | Jiang, He-Wei.,Czajkowsky, Daniel M..,Wang, Tao.,Wang, Xu-De.,Wang, Jia-bin.,...&Tao, Sheng-Ce.(2018).Identification of serine 119 as an effective inhibitor binding site of m. tuberculosis ubiquitin-like protein ligase pafa using purified proteins and m. smegmatis.Ebiomedicine,30,225-236. |
| MLA | Jiang, He-Wei,et al."Identification of serine 119 as an effective inhibitor binding site of m. tuberculosis ubiquitin-like protein ligase pafa using purified proteins and m. smegmatis".Ebiomedicine 30(2018):225-236. |
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来源：武汉病毒研究所
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