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

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). (1)H and (19)F NMR studies inform on the BBOX mechanism including by providing evidence for cooperativity between monomers in subst...

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Detalles Bibliográficos
Autores principales: Leśniak, Robert K., Rydzik, Anna M., Kamps, Jos J. A. G., Kahn, Amjad, Claridge, Timothy D. W., Schofield, Christopher J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927413/
https://www.ncbi.nlm.nih.gov/pubmed/31702759
http://dx.doi.org/10.1039/c9cc06466d
Descripción
Sumario: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). (1)H and (19)F NMR studies inform on the BBOX mechanism including by providing evidence for cooperativity between monomers in substrate/some inhibitor binding. The value of the (19)F NMR methods is demonstrated by their use in the design of new BBOX inhibitors.