Inhibitory sites in enzymes: Zinc removal and reactivation by thionein
Inhibitory sites in enzymes: Zinc removal and reactivation by thionein
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DOI：
10.1073/pnas.96.5.1936
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发表时间：
1999-03-02
影响因子：
11.1
通讯作者：
Fischer, EH
中科院分区：
文献类型：
--
作者：
Maret, W;Jacob, C;Fischer, EH
硫蛋白（T）以前没有从生物材料中分离出来。然而，它是通过在氧化还原条件下，特别是在硒化合物的存在下，从金属硫蛋白中除去锌而瞬时原位产生的。T非常迅速地激活一组酶，其中锌结合在抑制位点。该反应是选择性的，这从T不从锌金属酶的催化位点除去锌的事实是显而易见的。T瞬时逆转锌抑制与其已知的能力，结合在金属硫蛋白簇的形式七个锌原子的化学计量相称。锌的抑制作用比以前报道的要明显得多，解离常数在低纳摩尔范围内。因此，T是一种有效的内源性螯合剂，这表明存在一种迄今未知和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，从而显著增加活性。该系统的潜在意义得到了糖酵解和信号转导相关酶的操作演示的支持。
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.