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Enhancement of Insulin Action by bis(Acetylacetonato)oxovanadium(IV) Occurs through Uncompetitive Inhibition of Protein Tyrosine Phosphatase-IB

机译:通过蛋白质酪氨酸磷酸酶-1b的小竞争性抑制来提高双(乙酰丙酮酰基)氧化钒(IV)的增强

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We have examined the influence of 6w(acetylacetonato)oxo-vanadium(IV) [VO(acac)2] on the catalytic activity of protein tyrosine phosphatase-lB (PTP1B). In the presence of/7-nitro-phenylphosphate as the substrate, VO(acac)2 exhibited mixed inhibition. However, VO(acac)2 exhibited uncompetitive inhibition of the enzyme with the undecapeptide substrate DAD-EpYLIPQQG, in which the sequence corresponds to residues 988-998 of the epidermal growth factor receptor and pY indicates the phosphotyrosine residue. These results are consistent with our earlier observations, on the basis of phosphotyrosine immunobiots, showing that VO(acac)2 potentiates tyrosine phosphorylation of the insulin receptor synergistically with insulin Because uncompetitive inhibitors of PTP1B have not been described heretofore, we discuss the importance of uncompetitive inhibition with respect to design of inhibitors of the enzyme for therapeutic purposes.
机译:我们已经研究了6W(乙酰丙酮)氧代钒(IV)[VO(ACAC)2]对蛋白酪氨酸磷酸酶-1b(PTP1b)的催化活性的影响。在/ 7-硝基 - 苯基磷酸盐中作为底物,VO(ACAC)2表现出混合抑制。然而,VO(ACAC)2将酶与未捕获的肽底物Dad-Epylipqgg表现出对酶的外向抑制,其中序列对应于表皮生长因子受体的残基988-998,并且Py表示磷酸酪氨酸残基。这些结果与我们之前的观察结果一致,基于磷酸酪氨酸免疫直杆菌,表明VO(ACAC)2将胰岛素受体的酪氨酸磷酸化与胰岛素协同增强,因为PTP1B的未竞争性抑制剂尚未描述,我们讨论了非竞争力的重要性抑制酶抑制剂的抑制作用治疗目的。

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