Ejection of structural zinc leads to inhibition of γ-butyrobetaine hydroxylase.
نویسندگان
چکیده
γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate and Fe(II) dependent oxygenase that catalyses an essential step during carnitine biosynthesis in animals. BBOX is inhibited by ejection of structural zinc by a set of selenium containing analogues. Previous structural analyses indicated that an undisrupted N-terminal zinc binding domain of BBOX is required for catalysis. Ebselen is a relatively potent BBOX inhibitor, an observation which may in part reflect its cardioprotective properties.
منابع مشابه
Development and application of ligand - based NMR screening assays for γ - butyrobetaine hydroxylase † ‡
γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate (2OG) dependent oxygenase that catalyses the stereoselective C-3 hydroxylation of γ-butyrobetaine (GBB) to give L-carnitine. L-Carnitine is involved in fatty acid metabolism in all animals and in some prokaryotes, and BBOX is a current drug target for the treatment of myocardial infarction. We describe the development and application of H N...
متن کاملCation–π Interactions Contribute to Substrate Recognition in γ‐Butyrobetaine Hydroxylase Catalysis
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 anal...
متن کاملOxygenase-Catalyzed Desymmetrization of N,N-Dialkyl-piperidine-4-carboxylic Acids**
γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate dependent oxygenase that catalyzes the final hydroxylation step in the biosynthesis of carnitine. BBOX was shown to catalyze the oxidative desymmetrization of achiral N,N-dialkyl piperidine-4-carboxylates to give products with two or three stereogenic centers.
متن کاملCofactor Requirements of y=Butyrobetaine Hydroxylase from Rat Liver*
The hydroxylation of y-butyrobetaine (4-trimethylaminobutyrate) to carnitine (3-hydroxy-4-trimethylaminobutyrate) is catalyzed by a soluble enzyme from rat liver which has been partially purified. The enzyme which previously has been shown to require molecular oxygen and ferrous ion has a specific requirement for 2-ketoglutarate. Several reductams stimulate the formation of hydroxylated product...
متن کاملΓ-butyrobetaine as a Specific Antagonist for Carnitine in the Development of the Early Chick Embryo
The effect of gamma-butyrobetaine alone and with the addition of carnitine on the development of the early excised chick embryo has been studied. gamma-Butyrobetaine in appropriate amounts exerts an inhibitory effect which can be relieved or annulled by the inclusion of appropriate amounts of carnitine. This has been interpreted as a metabolite-antimetabolite relationship, in which the normal m...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Bioorganic & medicinal chemistry letters
دوره 24 21 شماره
صفحات -
تاریخ انتشار 2014