Protein phosphotyrosine phosphatase 1B: Structure, function, role in the development of metabolic disorders and their correction by the enzyme inhibitors

Resumo

Protein phosphotyrosine phosphatase 1B (PPTP1B) dephosphorylates receptor and nonreceptor forms of tyrosine kinases, causing the inhibition of their activity and thus regulating appropriate signaling cascades. Increased PPTP1B activity leads to insulin and leptin resistance, being among the causes of type 2 diabetes mellitus and many other metabolic and functional disorders. Selective PPTP1B inhibitors normalize functions of insulin, leptin and some other systems comprising different forms of tyrosine kinases as signaling components, and their development is a promising approach to treat and prevent metabolic disorders. Currently, an active search is in progress for “binary” PPTP1B inhibitors able to interact simultaneously with the catalytic and allosteric sites of the enzyme, providing thereby high efficiency and selectivity of their action. This review focuses on the status quo of the problem of studying the structure, functions and regulatory properties of PPTP1B, its role in the development of metabolic disorders, as well as on recent advances in designing selective PPTP1B inhibitors.