Cation-π Interactions Contribute to Substrate Recognition in γ-Butyrobetaine Hydroxylase Catalysis.
Cation-π Interactions Contribute to Substrate Recognition in γ-Butyrobetaine Hydroxylase Catalysis.
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DOI：
10.1002/chem.201503761
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发表时间：
2016-01-22
期刊：
影响因子：
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通讯作者：
Mecinović J
中科院分区：
文献类型：
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作者：
Kamps JJ;Khan A;Choi H;Lesniak RK;Brem J;Rydzik AM;McDonough MA;Schofield CJ;Claridge TD;Mecinović J
γ -丁甜菜碱羟化酶（BBOX）是一种非血红素FeII和2 -氧葡萄糖酸盐依赖性加氧酶，在肉毒碱生物合成的最后一步催化γ -丁甜菜碱（γ bb）未激活的C - H键的立体选择性羟基化。BBOX包含一个芳香笼，用于识别带正电的γBB底物的三甲基铵基团。三甲基铵基中P和As取代N的底物类似物的酶结合和动力学分析表明，这些类似物是良好的BBOX底物，遵循N+>P+>As+的效率趋势。结果表明，γ - bb的未带电碳类似物不是BBOX底物，从而突出了能量有利的阳离子-π相互作用在生产底物识别中的重要性。
γ‐Butyrobetaine hydroxylase (BBOX) is a non‐heme FeII‐ and 2‐oxoglutarate‐dependent oxygenase that catalyzes the stereoselective hydroxylation of an unactivated C−H bond of γ‐butyrobetaine (γBB) in the final step of carnitine biosynthesis. BBOX contains an aromatic cage for the recognition of the positively charged trimethylammonium group of the γBB substrate. Enzyme binding and kinetic analyses on substrate analogues with P and As substituting for N in the trimethylammonium group show that the analogues are good BBOX substrates, which follow the efficiency trend N+>P+>As+. The results reveal that an uncharged carbon analogue of γBB is not a BBOX substrate, thus highlighting the importance of the energetically favorable cation–π interactions in productive substrate recognition.