Zn2 +调节鸟氨酸transcarbamoylase。我的作用机制。
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李,沈WH,米勒啊,郭LC
Zn2 +调节鸟氨酸transcarbamoylase。我的作用机制。
J杂志。1990年1月5日,211 (1):255 - 69。
- PubMed ID
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2105398 (在PubMed]
- 文摘
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鸟氨酸transcarbamoylase催化形成L-citrulline[氨基甲酰磷酸和L-ornithine。合成代谢酶的大肠杆菌由三个相同的子单元和类似,主要和四级结构,天冬氨酸transcarbamoylase的催化装置。然而,鸟氨酸transcarbamoylase没有监管的子单元。尽管这种酶不绑定的基质,以合作、荧光光谱实验表明,锌增加了免费的变构酶。金属绑定过程是由酶的去质子化集团pKa小于7。金属离子的饱和约束曲线s形,收益率是希尔系数1.6在pH值8.5和25度c缺乏底物的情况下,进一步促进锌酶异构化缓慢,产生一阶速率常数的7最低为1;因此,金属是一个缓慢的、紧束缚抑制剂。异构化的酶活性,包含三个锌离子。首先绑定酶[氨基甲酰磷酸时,稳态动力学分析表明,锌再次本着合作的精神结合二进制酶复杂,希尔系数为1.5,但现在的金属离子的行为只是作为一个古典,可逆抑制剂;竞争对L-ornithine,非竞争性反对[氨基甲酰磷酸,诱发不酶异构化。 However, as a result of the competition between zinc and L-ornithine for the same site on the enzyme, the L-ornithine saturation curve becomes sigmoidal. Displacement of the allosteric zinc from the enzyme by L-ornithine is the cause of co-operative addition of this substrate. The combined results suggest that zinc regulates ornithine transcarbamoylase via two routes: (1) as an allosteric cofactor of the substrate-bound enzyme in mediating site-site interactions; and (2) as a slow, tight-binding inhibitor of the free enzyme in inducing inactivation. The concentration of zinc that is effective for action is in the micromolar range. The finding that E. coli ornithine transcarbamoylase can be induced to express co-operativity in binding its substrates has recently been confirmed by site-directed mutagenesis experiments. When the active site residue Arg106 is altered to a glycine, the resultant mutant enzyme exhibits both homotropic and heterotropic interactions towards its substrates. In view of the quaternary structure of holoenzyme aspartate transcarbamoylase, the "silent" co-operativity of ornithine transcarbamoylase is of particular interest in the study of evolution of complex, regulatory proteins.