Fig. 1. (A) Dimeric γ-butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate oxygenase. (B) BBOX inhibitors: Mildronate (4); isoquinoline (5). (C) Overlaid γ-butyrobetaine (GBB, 3; green sticks) and N-oxalylglycine (NOG; salmon sticks) binding residues of hBBOX (blue/orange cartoon (dimer view)) blue lines (PDB: ; 3O2G)1 and a psBBOX model23 (yellow lines). psBBOX Tyr201 (Y194 hBBOX,1 pink sticks) is involved in GBB quaternary ammonium ion recognition;24 it is located in a ‘flexible-loop’ region. (D) Titrations of (4) manifest only ∼60% GBB displacement using a 1H NMR reporter assay;25 by contrast (5) apparently displaces ∼90% GBB.
