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首页> 外文期刊>Biochemistry >Catalytic Mechanism of the Cyclohydrolase Activity of Human Aminoimidazole Carboxamide Ribonucleotide Formyltransferase/Inosine Monophosphate Cyclohydrolase
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Catalytic Mechanism of the Cyclohydrolase Activity of Human Aminoimidazole Carboxamide Ribonucleotide Formyltransferase/Inosine Monophosphate Cyclohydrolase

机译：人氨基咪唑羧酰胺核糖核苷酸甲酰基转移酶/ inosine单磷酸环旋水解酶环氧水解酶活性的催化机理

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摘要

The bifunctional enzyme aminoimidazole carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase (ATIC)is responsible for catalysis of the last two steps in the de novo purine pathway.Using recently determined crystal structures of ATIC as a guide,four candidate residues,Lys66,Tyr l04,Asp 125,and Lys l37,were identified for site-directed mutagenesis to study the cyclohydrolase activity of this bifunctional enzyme.Steady-state kinetic experiments on these mutants have shown that none of these residues are absolutely required for catalytic activity;however,they strongly influence the efficiency of the reaction.Since the FAICAR binding site is made up mostly of backbone interactions with highly conserved residues,we postulate that these conserved interactions orient FAICAR in the active site to favor the intramolecular ring closure reaction and that this reaction may be catalyzed by an orbital steering mechanism.Furthermore,it was shown that Lys l37 is responsible for the increase in cyclohydrolase activity for dimeric ATIC,which was reported previously by our laboratory.From the experiments presented here,a catalytic mechanism for the cyclohydrolase activity is postulated.
机译：双官能酶氨基咪唑羧酰胺核糖核苷酸转化酶/ InoSine单磷酸环旋解酶（ATIC）负责de Novo嘌呤途径的最后两个步骤的催化。最近确定的Atic晶体结构作为导向，四个候选残留物，Lys66，Tyr L04，鉴定Asp 125和Lys L37鉴定出定点诱变，以研究这种双官能酶的环烃酶活性。这些突变体上的稳定状态动力学实验表明，催化活性绝对需要这些残基绝对需要;然而，它们强烈影响反应的效率。食物组成的结合位点主要是与高度保守的残留物的骨干相互作用，我们假设这些保守的相互作用东方FAICAR在活性位点上有利于分子内闭合反应，并且该反应可能催化通过轨道转向机制。繁殖，显示LYS L37负责通过我们的实验室报道了二聚体atic的环氧化物酶活性的增加。从这里呈现的实验，假设环氧水解酶活性的催化机制。

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  • 来源
    《Biochemistry》 |2004年第5期|共9页
  • 作者

    James M.Vergis; G.Peter Beardsley;

  • 作者单位

    Department of Molecular Biophysics and Biochemistry Yale University New Haven Connecticut 06520 and Departments of Pharmacology and Pediatrics Yale University School of Medicine New Haven Connecticut 06520;

    Department of Molecular Biophysics and Biochemistry Yale University New Haven Connecticut 06520 and Departments of Pharmacology and Pediatrics Yale University School of Medicine New Haven Connecticut 06520;

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  • 正文语种 eng
  • 中图分类 生物化学;
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