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19F NMR studies on ?-butyrobetaine hydroxylase provide mechanistic insights and suggest a dual inhibition mode.

ABSTRACT: The final step in the biosynthesis of l-carnitine in humans is catalysed by the 2-oxoglutarate and ferrous iron dependent oxygenase, ?-butyrobetaine hydroxylase (BBOX). 1H and 19F NMR studies inform on the BBOX mechanism including by providing evidence for cooperativity between monomers in substrate/some inhibitor binding. The value of the 19F NMR methods is demonstrated by their use in the design of new BBOX inhibitors.

SUBMITTER: Lesniak RK

PROVIDER: S-EPMC6927413 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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19F NMR studies on γ-butyrobetaine hydroxylase provide mechanistic insights and suggest a dual inhibition mode.

Leśniak Robert K RK Rydzik Anna M AM Kamps Jos J A G JJAG Kahn Amjad A Claridge Timothy D W TDW Schofield Christopher J CJ

Chemical communications (Cambridge, England) 20191201 98

The final step in the biosynthesis of l-carnitine in humans is catalysed by the 2-oxoglutarate and ferrous iron dependent oxygenase, γ-butyrobetaine hydroxylase (BBOX). 1H and 19F NMR studies inform on the BBOX mechanism including by providing evidence for cooperativity between monomers in substrate/some inhibitor binding. The value of the 19F NMR methods is demonstrated by their use in the design of new BBOX inhibitors. ...[more]

PMID: 31702759

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