Different Modes of Inhibitor Binding to Prolyl Hydroxylase by Combined Use of X-ray Crystallography and NMR Spectroscopy of Paramagnetic Complexes

In aqueous solution, azaquinolone inhibitors bind to prolyl 4-hydroxylase in two different orientations, as first detected by 19F spectroscopy. This contrasts with the crystallographic structure where only one orientation has been determined. Dissection of the metal binding properties of the enzyme allowed structures of both complexes to be obtained in solution from 19F and 13C dipolar shifts in a labeled ligand.