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Structural Insight into the Mechanism of Staphylococcus aureus Stp1 Phosphatase

文献类型：期刊论文

作者Yang, Teng1,2; Liu, Tingting2,3; Gan, Jianhua4; Yu, Kunqian2,3; Chen, Kaixian2,3; Xue, Wei1; Lan, Lefu2,3; Yang, Song1; Yang, Cai-Guang2,3
刊名ACS INFECTIOUS DISEASES
出版日期2019-06-01
卷号5期号:6页码:841-850
关键词Stp1 phosphatase dephosphorylation crystal structure substrate recognition
ISSN号2373-8227
DOI10.1021/acsinfecdis.8b00316
通讯作者Yang, Song(jhzx.msm@gmail.com) ; Yang, Cai-Guang(yangcg@simm.ac.cn)
英文摘要Staphylococcus aureus Stp1, which belongs to the bacterial metal-dependent protein phosphatase (PPM) family, is a promising candidate for antivirulence targeting. How Stp1 recognizes the phosphorylated peptide remains unclear, however. In order to investigate the recognition mechanism of Stp1 in depth, we have determined a series of crystal structures of S. aureus Stp1 in different states and the structural complex of Stp1 bound with a phosphorylated peptide His12. Different phosphorylated peptides, including MgrA- and GraR-derived phosphopeptides, are substrates of Stp1, which supports the function of Stp1 as a selective Ser/Thr phosphatase. In addition, interestingly, the crystal structures of R161-Stp1 variants combined with the biochemical activity validations have uncovered that R161 residue plays a key role to control the conformation switches of the flap domain in order to facilitate substrate binding and the dephosphorylation process. Our findings provide crucial structural insight into the molecular mechanism of S. aureus Stp1 phosphatase and reveal the phosphorylated peptides for biochemistry study and inhibitor screening of Stp1.
WOS关键词BACTERIAL VIRULENCE ; 3RD METAL ; PHOSPHORYLATION ; INHIBITOR ; BINDING ; CONFORMATION ; EXPRESSION ; GROWTH
资助项目Science and Technology Commission Shanghai Municipality[17XD1404400] ; National Natural Science Foundation of China[81661138004] ; National Natural Science Foundation of China[81861138046] ; National Natural Science Foundation of China[21725801] ; National Natural Science Foundation of China[21877021]
WOS研究方向Pharmacology & Pharmacy ; Infectious Diseases
语种英语
WOS记录号WOS:000472120100007
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/289467]  
专题新药研究国家重点实验室
通讯作者Yang, Song; Yang, Cai-Guang
作者单位1.Guizhou Univ, State Key Lab Breeding Base Green Pesticide & Agr, Key Lab Green Pesticide & Agr Bioengn, Minist Educ,Ctr R&D Fine Chem, 2708 South Huaxi Rd, Guiyang 550025, Guizhou, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
4.Fudan Univ, Sch Life Sci, 2005 Songhu Rd, Shanghai 200433, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Teng,Liu, Tingting,Gan, Jianhua,et al. Structural Insight into the Mechanism of Staphylococcus aureus Stp1 Phosphatase[J]. ACS INFECTIOUS DISEASES,2019,5(6):841-850.
APA Yang, Teng.,Liu, Tingting.,Gan, Jianhua.,Yu, Kunqian.,Chen, Kaixian.,...&Yang, Cai-Guang.(2019).Structural Insight into the Mechanism of Staphylococcus aureus Stp1 Phosphatase.ACS INFECTIOUS DISEASES,5(6),841-850.
MLA Yang, Teng,et al."Structural Insight into the Mechanism of Staphylococcus aureus Stp1 Phosphatase".ACS INFECTIOUS DISEASES 5.6(2019):841-850.

入库方式： OAI收割

来源：上海药物研究所

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