Structural Insight into the Mechanism of Staphylococcus aureus Stp1 Phosphatase | |
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 |
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 |
DOI | 10.1021/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. |
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关键词 | BACTERIAL VIRULENCE ; 3RD METAL ; PHOSPHORYLATION ; INHIBITOR ; BINDING ; CONFORMATION ; EXPRESSION ; GROWTH |
WOS研究方向 | Pharmacology & Pharmacy ; Infectious Diseases |
语种 | 英语 |
出版者 | AMER CHEMICAL SOC |
WOS记录号 | WOS:000472120100007 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/289467] |
专题 | 中国科学院上海药物研究所 |
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. |
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