Inhibition of Low Molecular Weight Protein Tyrosine Phosphatase by an Induced-Fit Mechanism.
Inhibition of Low Molecular Weight Protein Tyrosine Phosphatase by an Induced-Fit Mechanism.
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DOI：
10.1021/acs.jmedchem.6b00993
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发表时间：
2016-10-13
影响因子：
7.3
通讯作者：
Zhang ZY
中科院分区：
文献类型：
--
作者：
He R;Wang J;Yu ZH;Zhang RY;Liu S;Wu L;Zhang ZY
The low molecular weight protein tyrosine phosphatase (LMW-PTP) is a regulator of a number of signaling pathways and has been implicated as a potential target for oncology and diabetes/obesity. There is significant therapeutic interest in developing potent and selective inhibitors to control LMW-PTP activity. We report the discovery of a novel class of LMW-PTP inhibitors derived from SulfoPhenyl Acetic Amide (SPAA), some of which exhibit greater than 50-fold preference for LMW-PTP over a large panel of PTPs. X-ray crystallography reveals that binding of SPAA-based inhibitors induces a striking conformational change in the LMW-PTP active site, leading to the formation of a previously undisclosed hydrophobic pocket to accommodate the α-phenyl ring in the ligand. This induced-fit mechanism is likely a major contributor responsible for the exquisite inhibitor selectivity.
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低分子量蛋白酪氨酸磷酸酶（LMWPTP）上调介导结直肠癌的恶性潜力。
影响因子：
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作者：
Hoekstra E;Kodach LL;Das AM;Ruela-de-Sousa RR;Ferreira CV;Hardwick JC;van der Woude CJ;Peppelenbosch MP;Ten Hagen TL;Fuhler GM
通讯作者：
Fuhler GM
影响因子：
2.9
作者：
Rigacci, Stefania;Guidotti, Valentina;Berti, Andrea
通讯作者：
Berti, Andrea
影响因子：
3.5
作者：
BURLEY, SK;PETSKO, GA
通讯作者：
PETSKO, GA
影响因子：
4.8
作者：
Pandey, Sanjay K.;Yu, Xing Xian;Bhanot, Sanjay
通讯作者：
Bhanot, Sanjay
影响因子：
3.5
作者：
Forghieri, Marco;Laggner, Christian;Costantino, Luca
通讯作者：
Costantino, Luca