title: Ejection of structural zinc leads to inhibition of γ-butyrobetaine hydroxylase.
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.
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Rydzik
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brem
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Weston B
authors.initials: WB
authors.lastname: Struwe
authors.affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus Roosvelt Drive, Headington OX3 7DQ, United Kingdom.
authors.forename: Grazyna T
authors.initials: GT
authors.lastname: Kochan
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Justin L P
authors.initials: JL
authors.lastname: Benesch
authors.affiliation: 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.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
mesh_terms: D001393:Azoles / Q000494:pharmacology*; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D054833:Isoindoles; D008958:Models, Molecular; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D015032:Zinc / Q000378:metabolism*; D050563:gamma-Butyrobetaine Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001393:Azoles; D004791:Enzyme Inhibitors; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D050563:gamma-Butyrobetaine Dioxygenase; D015032:Zinc
keywords: 2-Oxoglutarate dependent oxygenase; Carnitine; Ebselen; Zinc ejection; γ-Butyrobetaine hydroxylase