Zhao Z
Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
Biochem Biophys Res Commun. 1996 Jan 17;218(2):480-4. doi: 10.1006/bbrc.1996.0085.
Thiophosphorylated proteins or peptides are poor substrates of protein phosphatases. As a competitive inhibitor of a protein tyrosine phosphatase, a tyrosine-thiophosphorylated nonapeptide ENDYINASL displays a KI value of 0.25 microM, in comparison with the Km value of 3.1 microM exerted by the enzyme toward the phosphorylated form of the peptide. Furthermore, adenosine 5'-O-3-thiotriphosphate is also an effective competitive inhibitor of the enzyme with a KI value of 1.4 microM. In contrast, ATP and 5'-adenylimidodiphosphate are much less effective, indicating that the thiophosphate group plays a major role in the inhibition process. Further supporting this is the fact that sodium thiophosphate is a more effective inhibitor than inorganic phosphate (IC50 = 0.47 mM versus 15 mM). The inhibition by thiophosphate compounds is specific for PTPs. The data suggest the application of thiophosphate derivatives as specific inhibitors of PTPs.
硫代磷酸化的蛋白质或肽是蛋白磷酸酶的不良底物。作为一种蛋白酪氨酸磷酸酶的竞争性抑制剂，酪氨酸硫代磷酸化的九肽ENDYINASL的抑制常数（KI）值为0.25微摩尔，而该酶作用于磷酸化肽形式的米氏常数（Km）值为3.1微摩尔。此外，腺苷5'-O-3-硫代三磷酸也是该酶的有效竞争性抑制剂，抑制常数为1.4微摩尔。相比之下，ATP和5'-腺苷亚氨二磷酸的抑制效果要差得多，这表明硫代磷酸基团在抑制过程中起主要作用。硫代磷酸钠比无机磷酸盐是更有效的抑制剂这一事实（半数抑制浓度分别为0.47毫摩尔和15毫摩尔）进一步支持了这一点。硫代磷酸化合物的抑制作用对蛋白酪氨酸磷酸酶具有特异性。这些数据表明硫代磷酸衍生物可作为蛋白酪氨酸磷酸酶的特异性抑制剂。
