Structural Basis of Fullerene Derivatives as Novel Potent Inhibitors of Protein Tyrosine Phosphatase 1B: Insight into the Inhibitory Mechanism through Molecular Modeling Studies

2016 ◽  
Vol 56 (10) ◽  
pp. 2024-2034 ◽  
Author(s):  
Mengdan Qian ◽  
Yaming Shan ◽  
Shanshan Guan ◽  
Hao Zhang ◽  
Song Wang ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Structural Basis ◽  
Protein Tyrosine Phosphatase 1B ◽  
Inhibitory Mechanism ◽  
Fullerene Derivatives ◽  
Modeling Studies ◽  
Molecular Modeling Studies ◽  
Insight Into

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

Interaction of different prototropic species of an anticancer drug ellipticine with HSA and IgG proteins: multispectroscopic and molecular modeling studies

2015 ◽  
Vol 17 (26) ◽  
pp. 16937-16946 ◽  
Author(s):  
Raina Thakur ◽  
Anupam Das ◽  
Vandna Sharma ◽  
Chandan Adhikari ◽  
Kalyan Sundar Ghosh ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Blood Serum ◽  
Anticancer Drug ◽  
Carrier Proteins ◽  
Physiological Conditions ◽  
Modeling Studies ◽  
Molecular Modeling Studies ◽  
Insight Into

Studies on interactions between an anticancer alkaloid, ellipticine, and various carrier proteins in blood serum show tangible results to gain insight into the solubility and transport of the drug under physiological conditions.

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