scholarly journals SHP Family Protein Tyrosine Phosphatases Adopt Canonical Active-Site Conformations in the Apo and Phosphate-Bound States

2013 ◽  
Vol 20 (9) ◽  
pp. 1039-1048 ◽  
Author(s):  
Nilda Alicea-Velazquez ◽  
Titus Boggon
Keyword(s):  
Active Site ◽  
Bound States ◽  
Protein Tyrosine Phosphatases ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Family Protein

scholarly journals [Difluro(phosphono)methyl]phenylalanine-containing peptide inhibitors of protein tyrosine phosphatases

1999 ◽  
Vol 337 (2) ◽  
pp. 219-223 ◽  
Author(s):  
Sylvie DESMARAIS ◽  
Richard W. FRIESEN ◽  
Robert ZAMBONI ◽  
Chidambaram RAMACHANDRAN
Keyword(s):  
Active Site ◽  
Protein Tyrosine Phosphatases ◽  
Selective Inhibitor ◽  
Peptide Inhibitors ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine

Peptides containing the non-hydrolysable phosphotyrosine analogue 4-[difluro(phosphono)methyl]phenylalanine [Phe(CF2P)] were synthesized and tested as inhibitors of the protein tyrosine phosphatases (PTPs) PTP1B, CD45, PTPβ, LAR and SHP-1. We have identified peptides containing two adjacent Phe(CF2P) residues as potent inhibitors of PTPs. The tripeptide having the sequence Glu-Phe(CF2P)-Phe(CF2P) is a potent and selective inhibitor of PTP1B. This peptide inhibits PTP1B with an IC50 of 40 nM, which is at least 100-fold lower than with other PTPs. A second tripeptide, Pro-Phe(CF2P)-Phe(CF2P), is most potent against PTPβ, with an IC50 of 200 nM, and inhibits PTP1B with an IC50 of 300 nM. These data suggest that it is possible to develop selective, active-site-directed, reversible, potent inhibitors of PTPs.

scholarly journals Conformational Motions Regulate Phosphoryl Transfer in Related Protein Tyrosine Phosphatases

Science ◽  
2013 ◽  
Vol 341 (6148) ◽  
pp. 899-903 ◽  
Author(s):  
Sean K. Whittier ◽  
Alvan C. Hengge ◽  
J. Patrick Loria
Keyword(s):  
Active Site ◽  
Protein Tyrosine Phosphatases ◽  
Binding Pocket ◽  
Resonance Spectroscopy ◽  
Phosphoryl Transfer ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Leaving Group ◽  
Kinetics Of ◽  
Loop Motion

Many studies have implicated a role for conformational motions during the catalytic cycle, acting to optimize the binding pocket or facilitate product release, but a more intimate role in the chemical reaction has not been described. We address this by monitoring active-site loop motion in two protein tyrosine phosphatases (PTPs) using nuclear magnetic resonance spectroscopy. The PTPs, YopH and PTP1B, have very different catalytic rates; however, we find in both that the active-site loop closes to its catalytically competent position at rates that mirror the phosphotyrosine cleavage kinetics. This loop contains the catalytic acid, suggesting that loop closure occurs concomitantly with the protonation of the leaving group tyrosine and explains the different kinetics of two otherwise chemically and mechanistically indistinguishable enzymes.

scholarly journals Suramin Is an Active Site-directed, Reversible, and Tight-binding Inhibitor of Protein-tyrosine Phosphatases

1998 ◽  
Vol 273 (20) ◽  
pp. 12281-12287 ◽  
Author(s):  
Yan-Ling Zhang ◽  
Yen-Fang Keng ◽  
Yu Zhao ◽  
Li Wu ◽  
Zhong-Yin Zhang
Keyword(s):  
Active Site ◽  
Tight Binding ◽  
Protein Tyrosine Phosphatases ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine

Thiophosphorylated Substrate Analogs Are Potent Active Site-Directed Inhibitors of Protein-Tyrosine Phosphatases

1994 ◽  
Vol 223 (1) ◽  
pp. 51-58 ◽  
Author(s):  
K.T. Hiriyanna ◽  
D. Baedke ◽  
K.H. Baek ◽  
B.A. Forney ◽  
G. Kordiyak ◽  
...  
Keyword(s):  
Active Site ◽  
Protein Tyrosine Phosphatases ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Substrate Analogs
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