INTERACTION OF HUMAN DNA POLYMERASE-BETA WITH IONS OF COPPER, LEAD, AND CADMIUM
INTERACTION OF HUMAN DNA POLYMERASE-BETA WITH IONS OF COPPER, LEAD, AND CADMIUM
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DOI：
10.1016/0003-9861(79)90557-5
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发表时间：
1979-01-01
影响因子：
3.9
通讯作者：
SCHMAELER, MA
中科院分区：
文献类型：
--
作者：
POPENOE, EA;SCHMAELER, MA
在适当的条件下，Cu 2+、Pb 2+和Cd 2+显著抑制人DNA聚合酶β。浓度低于10-5 M。每种金属相对于模板引物和脱氧核苷三磷酸底物均表现出明显的线性非竞争性抑制动力学，这表明与这些组分形成的复合物并不能解释抑制作用。显然，Pb 2+和Cd 2+都不通过从聚合酶中置换所需的Zn原子来抑制。金属与酶的相互作用可以被EDTA或硫醇化合物逆转或阻止，除了Cd 2+离子的抑制可以被单硫醇逆转，但不能被二硫醇逆转。金属可能不会通过与硫醇基团反应而抑制，因为用N-乙基马来酰亚胺预处理酶不会降低抑制作用。虽然Zn 2+在Mng活化的聚（dT）在聚（dA）模板上的合成中是中等抑制性的，但它可以满足对二价金属离子的要求，并且在测试的条件下，其有效性为Mn 2+的约60%。
Under appropriate conditions, Cu2+, Pb2+ and Cd2+ significantly inhibit human DNA polymerase .beta. at concentrations below 10-5 M. Each metal showed apparent linear noncompetitive inhibition kinetics with respect to the template primer and the deoxynucleoside triphosphate substrate, indicating that complex formation with these components does not account for the inhibition. Apparently, neither Pb2+ nor Cd2+ inhibit by displacing required Zn atoms from the polymerase. The interaction of the metals with the enzyme can be reversed or prevented by EDTA or by thiol compounds, except that inhibition by Cd2+ ions can be reversed by monothiols but not by dithiols. The metals probably do not inhibit through reaction with thiol groups since the inhibition is not decreased by pretreating the enzyme with N-ethylmaleimide. Although Zn2+ is moderately inhibitory in Mng activated poly(dT) synthesis on a poly(dA) template, it can fill the requirement for a divalent metal ion and, under the conditions tested, is about 60% as effective as Mn2+.