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Bioorg Med Chem Lett. 2014 Nov 1;24(21):4954-7. doi: 10.1016/j.bmcl.2014.09.035. Epub 2014 Sep 19.

Ejection of structural zinc leads to inhibition of γ-butyrobetaine hydroxylase.

Author information

1
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
2
Structural Genomics Consortium, University of Oxford, Old Road Campus Roosvelt Drive, Headington OX3 7DQ, United Kingdom.
3
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom. Electronic address: christopher.schofield@chem.ox.ac.uk.

Abstract

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.

KEYWORDS:

2-Oxoglutarate dependent oxygenase; Carnitine; Ebselen; Zinc ejection; γ-Butyrobetaine hydroxylase

PMID:
25266780
DOI:
10.1016/j.bmcl.2014.09.035
[Indexed for MEDLINE]

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