Kamps Jos J A G, Khan Amjad, Choi Hwanho, Lesniak Robert K, Brem Jürgen, Rydzik Anna M, McDonough Michael A, Schofield Christopher J, Claridge Timothy D W, Mecinović Jasmin
Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands.
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
Chemistry. 2016 Jan 22;22(4):1270-6. doi: 10.1002/chem.201503761. Epub 2015 Dec 14.
γ-Butyrobetaine hydroxylase (BBOX) is a non-heme Fe(II) - 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.
γ-丁基甜菜碱羟化酶（BBOX）是一种非血红素铁（II）和2-氧代戊二酸依赖性加氧酶，在肉碱生物合成的最后一步催化γ-丁基甜菜碱（γBB）未活化C-H键的立体选择性羟基化反应。BBOX含有一个芳香笼，用于识别γBB底物带正电荷的三甲基铵基团。对三甲基铵基团中用P和As取代N的底物类似物进行的酶结合和动力学分析表明，这些类似物是良好的BBOX底物，遵循效率趋势N(+) >P(+) >As(+)。结果表明，γBB的不带电荷的碳类似物不是BBOX底物，从而突出了在有效底物识别中能量有利的阳离子-π相互作用的重要性。
