Cation–π Interactions Contribute to Substrate Recognition in γ‐Butyrobetaine Hydroxylase Catalysis |
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| Authors: | Jos J A G Kamps Amjad Khan Dr Hwanho Choi Robert K Lesniak Dr Jürgen Brem Dr Anna M Rydzik Dr Michael A McDonough Prof Christopher J Schofield Prof Timothy D W Claridge Dr Jasmin Mecinovi? |
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| Institution: | 1. Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands;2. Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, UK |
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| Abstract: | 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. |
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| Keywords: | cation– pi interactions C− H oxidation enzyme catalysis molecular recognition oxygenases |
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