Fig. 3: Ligand-binding pocket of full-length Rat-KMO with inhibitors.
From: Full-length in meso structure and mechanism of rat kynurenine 3-monooxygenase inhibition
A, B Ligand-binding pocket of Rat-KMO inhibited by compound 3. Residues of α12 play key roles in compound 3 recognition. Key residues for compound 3 recognition are depicted as sticks. Sticks and secondary structures are coloured using the same scheme as that in Fig. 1. Hydrogen bonds are shown as broken lines. Detailed interactions are shown using MOE software. C Sequence alignment of the KMO C-terminal residues among species. R380 is K380 in human KMO. Discrepancies in the sequence at this region may explain the species differences observed in our pharmacological assays. D Surface plasmon resonance study of compound 3 shows a remarkably low koff value. E, F Crystal structure of Rat-KMO in complex with compound 4. Y398 was flipped to accommodate the methyl group and the isoindoline ring of compound 4, and protruded into a site perpendicular to and above FAD. Key residues and secondary structures are coloured using the same scheme as that in Fig. 1. Compound 4 is shown as green sticks.
