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Cation–π Interactions Contribute to Substrate Recognition in γ‐Butyrobetaine Hydroxylase Catalysis
Author(s) -
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
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201503761
Subject(s) - hydroxylation , substrate (aquarium) , chemistry , stereochemistry , stereoselectivity , enzyme , catalysis , heme , substrate specificity , oxygenase , biochemistry , biology , ecology
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.