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首页> 外文期刊>Biochemistry >Characterization of a Mutant Bacillus subtilis Adenylosuccinate Lyase Equivalent to a Mutant Enzyme Found in Human Adenylosuccinate Lyase Deficiency: Asparagine 276 Plays an Important Structural Role.
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Characterization of a Mutant Bacillus subtilis Adenylosuccinate Lyase Equivalent to a Mutant Enzyme Found in Human Adenylosuccinate Lyase Deficiency: Asparagine 276 Plays an Important Structural Role.

机译：枯草芽孢杆菌枯草芽孢杆菌腺苷琥珀酸酯裂解酶的等同于在人腺苷琥珀酸酯裂解酶缺乏症中发现的突变酶的特征：天冬酰胺276发挥重要的结构作用。

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Adenylosuccinate lyase, an enzyme catalyzing two reactions in purine biosynthesis (the cleavage of either adenylosuccinate or succinylaminoimidazole carboxamide ribotide), has been implicated in a human disease arising from point mutations in the gene encoding the enzyme. Asn(276) of Bacillus subtilis adenylosuccinate lyase, a residue corresponding to the location of a human enzyme mutation, was replaced by Cys, Ser, Ala, Arg, and Glu. The mutant enzymes exhibit decreased V(max) values (2-400-fold lower) for both substrates compared to the wild-type enzyme and some changes in the pH dependence of V(max) but no loss in affinity for adenylosuccinate. Circular dichroism reveals no difference in secondary structure between the wild-type and mutant enzymes. We show here for the first time that wild-type adenylosuccinate lyase exhibits a protein concentration dependence of molecular weight, secondary structure, and specific activity. An equilibrium constant between the dimer and tetramer was measured by light scattering for the wild-type and mutant enzymes. The equilibrium is somewhat shifted toward the tetramer in the mutant enzymes. The major difference between the wild-type and mutant enzymes appears to be in quaternary structure, with many mutant enzymes exhibiting marked thermal instability relative to the wild-type enzyme. We propose that mutations at position 276 result in structurally impaired adenylosuccinate lyases which are assembled into defective tetramers.
机译：腺嘌呤琥珀酸裂合酶是一种催化嘌呤生物合成中两个反应（腺苷琥珀酸或琥珀酰氨基咪唑羧酰胺核糖核苷酸的裂解）的酶，与编码该酶的基因中的点突变引起的人类疾病有关。枯草芽孢杆菌腺苷琥珀酸裂解酶的Asn（276）残基对应于人类酶突变的位置，被Cys，Ser，Ala，Arg和Glu取代。与野生型酶相比，两种底物的突变酶均显示出降低的V（max）值（降低2-400倍），并且V（max）的pH依赖性发生了一些变化，但对腺苷酸琥珀酸酯的亲和力却没有降低。圆二色性显示野生型和突变型酶之间的二级结构没有差异。我们在这里首次显示野生型腺苷酸琥珀酸裂合酶表现出分子量，二级结构和比活性的蛋白质浓度依赖性。通过光散射测定野生型和突变型酶的二聚体和四聚体之间的平衡常数。在突变酶中，平衡有些向四聚体移动。野生型和突变型酶之间的主要差异似乎在于四级结构，许多突变型酶相对于野生型酶表现出明显的热不稳定性。我们提出在276位的突变导致结构受损的腺苷琥珀酸裂合酶，其组装成有缺陷的四聚体。

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