Structure and Molecular Dynamics Simulations of Protein Tyrosine Phosphatase Non-Receptor 12 Provide Insights into the Catalytic Mechanism of the Enzyme

被引：9

作者：

Dong, Hui ^{[1
,2
]}

Zonta, Francesco ^{[3
]}

Wang, Shanshan ^{[3
]}

Song, Ke ^{[3
]}

He, Xin ^{[1
,2
]}

He, Miaomiao ^{[3
,4
,5
]}

Nie, Yan ^{[3
]}

Li, Sheng ^{[3
]}

机构：

[1] Chinese Acad Med Sci, Inst Radiat Med, Key Lab Tianjin Radiat & Mol Nucl Med, Tianjin 300192, Peoples R China

[2] Peking Union Med Coll, Tianjin 300192, Peoples R China

[3] ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China

[4] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[5] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2018年 / 19卷 / 01期

基金：

中国国家自然科学基金;

关键词：

PTPN12; molecular dynamics; structure; CELL LUNG-CANCER; CRYSTAL-STRUCTURE; AUTOIMMUNE-DISEASES; FORCE-FIELD; PTP-PEST; INHIBITOR; 1B; SPECIFICITY; HEALTH; INTERMEDIATE;

D O I：

10.3390/ijms19010060

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Protein tyrosine phosphatase non-receptor 12 (PTPN12) is an important protein tyrosine phosphatase involved in regulating cell adhesion and migration as well as tumorigenesis. Here, we solved a crystal structure of the native PTPN12 catalytic domain with the catalytic cysteine (residue 231) in dual conformation (phosphorylated and unphosphorylated). Combined with molecular dynamics simulation data, we concluded that those two conformations represent different states of the protein which are realized during the dephosphorylation reaction. Together with docking and mutagenesis data, our results provide a molecular basis for understanding the catalytic mechanism of PTPN12 and its role in tumorigenesis.

引用

页数：14

共 45 条

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