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Cation-? Interactions Contribute to Substrate Recognition in ?-Butyrobetaine Hydroxylase Catalysis.

ABSTRACT: ?-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 ?-butyrobetaine (?BB) in the final step of carnitine biosynthesis. BBOX contains an aromatic cage for the recognition of the positively charged trimethylammonium group of the ?BB 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 ?BB is not a BBOX substrate, thus highlighting the importance of the energetically favorable cation-? interactions in productive substrate recognition.

SUBMITTER: Kamps JJ

PROVIDER: S-EPMC4736438 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Cation-π Interactions Contribute to Substrate Recognition in γ-Butyrobetaine Hydroxylase Catalysis.

Kamps Jos J A G JJ Khan Amjad A Choi Hwanho H Lesniak Robert K RK Brem Jürgen J Rydzik Anna M AM McDonough Michael A MA Schofield Christopher J CJ Claridge Timothy D W TD Mecinović Jasmin J

Chemistry (Weinheim an der Bergstrasse, Germany) 20151214 4

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 t ...[more]

PMID: 26660433

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