5x6q

Crystal structure of Pseudomonas fluorescens KMO in complex with Ro 61-8048

spinqualitylabelsall models 5x6q, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5x6q is a 1 chain structure with sequence from Pseudomonas fluorescens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.897Å Ligands: 7ZR, FAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KMO_PSEFL Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Probably required for the synthesis of quinolinic acid and the siderophore quinolobactin. Publication Abstract from PubMed Kynurenine 3-monooxygenase (KMO) inhibitors have been developed for the treatment of neurodegenerative disorders. The mechanisms of flavin reduction and hydrogen peroxide production by KMO inhibitors are unknown. Herein, we report the structure of human KMO and crystal structures of Saccharomyces cerevisiae (sc) and Pseudomonas fluorescens (pf) KMO with Ro 61-8048. Proton transfer in the hydrogen bond network triggers flavin reduction in p-hydroxybenzoate hydroxylase, but the mechanism triggering flavin reduction in KMO is different. Conformational changes via pi-pi interactions between the loop above the flavin and substrate or non-substrate effectors lead to disorder of the C-terminal alpha helix in scKMO and shifts of domain III in pfKMO, stimulating flavin reduction. Interestingly, Ro 61-8048 has two different binding modes. It acts as a competitive inhibitor in scKMO and as a non-substrate effector in pfKMO. These findings provide understanding of the catalytic cycle of KMO and insight for structure-based drug design of KMO inhibitors. Structural Basis for Inhibitor-Induced Hydrogen Peroxide Production by Kynurenine 3-Monooxygenase.,Kim HT, Na BK, Chung J, Kim S, Kwon SK, Cha H, Son J, Cho JM, Hwang KY Cell Chem Biol. 2018 Feb 1. pii: S2451-9456(18)30030-8. doi:, 10.1016/j.chembiol.2018.01.008. PMID:29429898 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monooxygenase 3D structures

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