3ng7

Complex of dithionite-reduced 6-hydroxy-L-nicotine oxidase with substrate bound at active site and inhibitor at exit cavity

spinqualitylabelsall models 3ng7, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ng7 is a 1 chain structure with sequence from Paenarthrobacter nicotinovorans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: FAD, GP7, HNK, HNL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HLNO_PAENI Involved in the degradation of L-nicotine (PubMed:5849820). Catalyzes the oxidation of (S)-6-hydroxynicotine (6-hydroxy-L-nicotine) to 6-hydroxypseudooxynicotine (PubMed:5849820, PubMed:4965794, PubMed:5646150, PubMed:21383134, PubMed:26744768, PubMed:28080034). Oxidation of the pyrrolidine ring of (S)-6-hydroxynicotine leads to the formation of the optically inactive 6-hydroxy-N-methylmyosmine, which hydrolyzes spontaneously to 6-hydroxypseudooxynicotine (PubMed:4965794, PubMed:21383134, PubMed:26744768, PubMed:28080034). Acts with absolute stereospecificity on the L-form of 6-hydroxynicotine (PubMed:4965794). Can also use (S)-6-hydroxynornicotine (PubMed:26744768, PubMed:28080034). Publication Abstract from PubMed FAD-linked oxidases constitute a class of enzymes which catalyze dehydrogenation as a fundamental biochemical reaction, followed by reoxidation of reduced flavin. Here, we present high-resolution crystal structures showing the flavoenzyme 6-hydroxy-l-nicotine oxidase in action. This enzyme was trapped during catalytic degradation of the native substrate in a sequence of discrete reaction states corresponding to the substrate-reduced enzyme, a complex of the enzyme with the intermediate enamine product and formation of the final aminoketone product. The inactive d-stereoisomer binds in mirror symmetry with respect to the catalytic axis, revealing absolute stereospecificity of hydrogen transfer to the flavin. The structural data suggest deprotonation of the substrate when bound at the active site, an overall binary complex mechanism and oxidation by direct hydride transfer. The amine nitrogen has a critical role in the dehydrogenation step and may activate carbocation formation at the alpha-carbon via delocalization from the lone pair to sigma* C(alpha)-H. Enzymatically assisted hydrolysis of the intermediate product occurs at a remote (P site) cavity. Substrate entry and product exit follow different paths. Structural and kinetic data suggest that substrate can also bind to the reduced enzyme, associated with slower reoxidation as compared to the rate of reoxidation of free enzyme. The results are of general relevance for the mechanisms of flavin amine oxidases. Crystallographic snapshots of the complete reaction cycle of nicotine degradation by an amine oxidase of the monoamine oxidase (MAO) family.,Kachalova G, Decker K, Holt A, Bartunik HD Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4800-5. Epub 2011 Mar 7. PMID:21383134 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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