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首页> 外文期刊>Chemistry: A European journal >Computational mutation analysis of hydrogen abstraction and radical rearrangement steps in the catalysis of coenzyme B-12-dependent diol dehydratase
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Computational mutation analysis of hydrogen abstraction and radical rearrangement steps in the catalysis of coenzyme B-12-dependent diol dehydratase

机译：辅酶B-12依赖性二醇脱水酶催化过程中氢提取和自由基重排步骤的计算突变分析

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摘要

A mutation analysis of the catalytic functions of active-site residues of coenzyme B-12-dependent diol dehydratase in the conversion of 1,2-propanediol to 1,1-propanediol has been carried out by using QM/MM computations. Mutants His-143A1a, Glu170Gln, Glu170Ala, and Glu170Ala/Glu221Ala were considered to estimate the impact of the mutations of His143 and Glu170. In the His143Ala mutant the activation energy for OH migration increased to 16.4 from 11.5 kcal mol(-1) in the wildtype enzyme. The highest activation energy. 19.6 kcal mol(-1), was measured for hydrogen back-abstraction in this reaction. The transition state for OH migration is not sufficiently stabilized by the hydrogen-bonding interaction formed between the spectator OH group and Gln170 in the Glu170Gln mutant, which demonstrates that a strong proton acceptor is required to promote OH migration. In the Glu170Ala mutant, a new strong hydrogen bond is formed between the spectator OH group and Glu221. A computed activation energy of 13.6 kcal mol(-1) for OH migration in the Glu170Ala mutant is only 2.1 kcal mol(-1) higher than the corresponding barrier in the wild-type enzyme. Despite the low activation barrier, the Glu170Ala mutant is inactive because the subsequent hydrogen back-abstraction is energetically demanding in this mutant. OH migration is not feasible in the Glu170Ala/Glu221Ala mutant because the activation barrier for OH migration is greatly increased by the loss of COO- groups near the spectator OH group. This result indicates that the effect of partial deprotonation of the spectator OH group is the most important factor in reducing the activation barrier for OH migration in the conversion of 1,2-propanediol to 1,1-propanediol catalyzed by diol dehydratase.
机译：通过使用QM / MM计算，对辅酶B-12依赖性二醇脱水酶的活性位点残基在1,2-丙二醇向1,1-丙二醇的转化中的催化功能进行了突变分析。突变体His-143A1a，Glu170Gln，Glu170Ala和Glu170Ala / Glu221Ala被认为可评估His143和Glu170突变的影响。在His143Ala突变体中，OH迁移的活化能从野生型酶中的11.5 kcal mol（-1）增加到16.4。最高的活化能。在此反应中测量了19.6 kcal mol（-1）的氢反吸收。观众OH基团与Glu170Gln突变体中的Gln170之间形成的氢键相互作用不能充分稳定OH迁移的过渡态，这表明需要强质子受体来促进OH迁移。在Glu170Ala突变体中，旁观者OH基团与Glu221之间形成了一个新的强氢键。对于Glu170Ala突变体中的OH迁移，计算出的活化能为13.6 kcal mol（-1）仅比野生型酶中的相应屏障高2.1 kcal mol（-1）。尽管激活势垒较低，但Glu170Ala突变体仍处于失活状态，因为在此突变体中需要大量的后续氢反吸收。 OH迁移在Glu170Ala / Glu221Ala突变体中不可行，因为OH迁移的激活壁垒因旁观者OH基团附近的COO-基团的丢失而大大增加。该结果表明，在二醇脱水酶催化的1，2-丙二醇向1，1-丙二醇的转化中，旁观者OH基团的部分去质子化的影响是减少OH迁移的活化障碍的最重要因素。

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