Structural highlights
Function
[PPAC_HUMAN] Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates. Isoform 3 does not possess phosphatase activity.
Publication Abstract from PubMed
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 alpha-phenyl ring in the ligand. This induced-fit mechanism is likely a major contributor responsible for the exquisite inhibitor selectivity.
Inhibition of Low Molecular Weight Protein Tyrosine Phosphatase by an Induced-Fit Mechanism.,He R, Wang J, Yu ZH, Zhang RY, Liu S, Wu L, Zhang ZY J Med Chem. 2016 Oct 3. PMID:27676368[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ He R, Wang J, Yu ZH, Zhang RY, Liu S, Wu L, Zhang ZY. Inhibition of Low Molecular Weight Protein Tyrosine Phosphatase by an Induced-Fit Mechanism. J Med Chem. 2016 Oct 3. PMID:27676368 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b00993
