Structural Basis of Plasticity in Protein Tyrosine Phosphatase 1B Substrate Recognition†,‡

Biochemistry ◽  
2000 ◽  
Vol 39 (28) ◽  
pp. 8171-8179 ◽  
Author(s):  
Mauro Sarmiento ◽  
Yoram A. Puius ◽  
Stefan W. Vetter ◽  
Yen-Fang Keng ◽  
Li Wu ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Substrate Recognition ◽  
Structural Basis ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine

scholarly journals Structural Basis for Inhibition of Protein-tyrosine Phosphatase 1B by Isothiazolidinone Heterocyclic Phosphonate Mimetics

2006 ◽  
Vol 281 (43) ◽  
pp. 32784-32795 ◽  
Author(s):  
Paul J. Ala ◽  
Lucie Gonneville ◽  
Milton C. Hillman ◽  
Mary Becker-Pasha ◽  
Min Wei ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Structural Basis ◽  
Side Chain ◽  
Protein Tyrosine Phosphatase 1B ◽  
Phosphate Binding ◽  
Protein Tyrosine ◽  
Starting Point ◽  
Network Of Hydrogen Bonds ◽  
Orthogonal Orientation

Crystal structures of protein-tyrosine phosphatase 1B in complex with compounds bearing a novel isothiazolidinone (IZD) heterocyclic phosphonate mimetic reveal that the heterocycle is highly complementary to the catalytic pocket of the protein. The heterocycle participates in an extensive network of hydrogen bonds with the backbone of the phosphate-binding loop, Phe182 of the flap, and the side chain of Arg221. When substituted with a phenol, the small inhibitor induces the closed conformation of the protein and displaces all waters in the catalytic pocket. Saturated IZD-containing peptides are more potent inhibitors than unsaturated analogs because the IZD heterocycle and phenyl ring directly attached to it bind in a nearly orthogonal orientation with respect to each other, a conformation that is close to the energy minimum of the saturated IZD-phenyl moiety. These results explain why the heterocycle is a potent phosphonate mimetic and an ideal starting point for designing small nonpeptidic inhibitors.

Structural Basis for Inhibition of the Protein Tyrosine Phosphatase 1B by Phosphotyrosine Peptide Mimetics†,‡

Biochemistry ◽  
1998 ◽  
Vol 37 (51) ◽  
pp. 17773-17783 ◽  
Author(s):  
Matthew R. Groves ◽  
Zhu-Jun Yao ◽  
Peter P. Roller ◽  
Terrence R. Burke, ◽  
David Barford
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Structural Basis ◽  
Peptide Mimetics ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine

Inhibition of Protein Tyrosine Phosphatase 1B by Lutein Derivatives isolated from Mexican Oregano (Lippia graveolens)

2018 ◽  
Vol 17 (3) ◽  
pp. 134-139
Author(s):  
R.M. Perez-Gutierrez
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Inhibitory Activity ◽  
Spectroscopic Data ◽  
Methanol Extract ◽  
Tyrosine Phosphatase ◽  
Positive Control ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Ic50 Value ◽  
Ic50 Values

Methanol extract from Lippia graveolens (Mexican oregano) was studied in order to identify inhibitory bioactives for protein tyrosine phosphatase 1B (PTP1B). Known flavone as lutein (1), and another flavone glycoside such as lutein-7-o-glucoside (2), 6-hydroxy-lutein-7-ohexoside (3) and lutein-7-o-ramnoide (4) were isolated from methanol extract of aerial parts of the Lippia graveolens. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR, MS and compared with spectroscopic data previously reported. These flavones were evaluated for PTP1B inhibitory activity. Among them, compounds 1 and 3 displayed potential inhibitory activity against PTP1B with IC50 values of 7.01 ± 1.25 μg/ml and 18.4 μg/ml, respectively. In addition, compound 2 and 4 showed moderate inhibitory activity with an IC50 value of 23.8 ± 6.21 and 67.8 ± 5.80 μg/ml respectively. Among the four compounds, luteolin was found to be the most potent PTP1B inhibitor compared to the positive control ursolic acid, with an IC50 value of 8.12 ± 1.06 μg/ml. These results indicate that flavonoids constituents contained in Lippia graveolens can be considered as a natural source for the treatment of type 2 diabetes.

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