Radical Reaction Control in the AdoMet Radical Enzyme CDG Synthase (QueE): Consolidate, Destabilize, Accelerate.
Radical Reaction Control in the AdoMet Radical Enzyme CDG Synthase (QueE): Consolidate, Destabilize, Accelerate.
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DOI：
10.1002/chem.201604719
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发表时间：
2017-01-18
期刊：
影响因子：
--
通讯作者：
Croft AK
中科院分区：
文献类型：
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作者：
Jäger CM;Croft AK
控制自由基中间体，从而催化和指导复杂的自由基反应是S -腺苷甲硫氨酸（SAM）依赖性自由基酶的核心特征。我们报告了从头算和DFT计算，强调了离子络合的特定影响，包括Mg2+，被认为是7 -羧基- 7 -脱氮鸟嘌呤合成酶（QueE）自由基稳定性和反应控制的关键催化成分。酶催化6 -羧基四氢蝶呤（CPH4）重排的关键中间体的自由基稳定能（RSEs）和自由基时钟样模型系统揭示了Mg2+在破坏底物衍生的自由基和相应副反应中的直接作用，实验观察到的重排在可能的替代反应中占据主导地位。重要的是，这是在对底物本身热力学破坏最小的情况下实现的，为酶提供了一种既保持结合势又加速重排步骤的新机制。其他的一价和二价离子被探测，只有指示的物种达到必要的自由基构象，以促进反应。
Controlling radical intermediates and thus catalysing and directing complex radical reactions is a central feature of S‐adensosylmethionine (SAM)‐dependent radical enzymes. We report ab initio and DFT calculations highlighting the specific influence of ion complexation, including Mg2+, identified as a key catalytic component on radical stability and reaction control in 7‐carboxy‐7‐deazaguanine synthase (QueE). Radical stabilisation energies (RSEs) of key intermediates and radical clock‐like model systems of the enzyme‐catalysed rearrangement of 6‐carboxytetrahydropterin (CPH4), reveals a directing role of Mg2+ in destabilising both the substrate‐derived radical and corresponding side reactions, with the effect that the experimentally‐observed rearrangement becomes dominant over possible alternatives. Importantly, this is achieved with minimal disruption of the thermodynamics of the substrate itself, affording a novel mechanism for an enzyme to both maintain binding potential and accelerate the rearrangement step. Other mono and divalent ions were probed with only dicationic species achieving the necessary radical conformation to facilitate the reaction.