Maret W, Jacob C, Vallee B L, Fischer E H
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Seeley G. Mudd Building, 250 Longwood Avenue, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1936-40. doi: 10.1073/pnas.96.5.1936.
Thionein (T) has not been isolated previously from biological material. However, it is generated transiently in situ by removal of zinc from metallothionein under oxidoreductive conditions, particularly in the presence of selenium compounds. T very rapidly activates a group of enzymes in which zinc is bound at an inhibitory site. The reaction is selective, as is apparent from the fact that T does not remove zinc from the catalytic sites of zinc metalloenzymes. T instantaneously reverses the zinc inhibition with a stoichiometry commensurate with its known capacity to bind seven zinc atoms in the form of clusters in metallothionein. The zinc inhibition is much more pronounced than was previously reported, with dissociation constants in the low nanomolar range. Thus, T is an effective, endogenous chelating agent, suggesting the existence of a hitherto unknown and unrecognized biological regulatory system. T removes the metal from an inhibitory zinc-specific enzymatic site with a resultant marked increase of activity. The potential significance of this system is supported by the demonstration of its operations in enzymes involved in glycolysis and signal transduction.
硫蛋白（T）此前尚未从生物材料中分离出来。然而，在氧化还原条件下，特别是在硒化合物存在的情况下，通过从金属硫蛋白中去除锌，可在原位瞬时生成硫蛋白。T能非常迅速地激活一组酶，在这些酶中锌结合在抑制位点上。该反应具有选择性，这从T不会从锌金属酶的催化位点去除锌这一事实中可以明显看出。T能以与其已知在金属硫蛋白中以簇状形式结合七个锌原子的能力相称的化学计量比，瞬间逆转锌抑制作用。锌抑制作用比以前报道的更为显著，解离常数处于低纳摩尔范围。因此，T是一种有效的内源性螯合剂，这表明存在一个迄今未知且未被认识的生物调节系统。T从抑制性锌特异性酶位点去除金属，从而导致活性显著增加。该系统在参与糖酵解和信号转导的酶中的作用得到证实，这支持了该系统的潜在重要性。
