title: Structural Analysis Provides Mechanistic Insight into Nicotine Oxidoreductase from Pseudomonas putida.
abstract: The first structure of nicotine oxidoreductase (NicA2) was determined by X-ray crystallography. Pseudomonas putida has evolved nicotine-degrading activity to provide a source of carbon and nitrogen. The structure establishes NicA2 as a member of the monoamine oxidase family. Residues 1-50 are disordered and may play a role in localization. The nicotine-binding site proximal to the isoalloxazine ring of flavin shows an unusual composition of the classical aromatic cage (W427 and N462). The active site architecture is consistent with the proposed binding of the deprotonated form of the substrate and the flavin-dependent oxidation of the pyrrolidone C-N bond followed by nonenzymatic hydrolysis.
authors.affiliation: Program in Biomolecular Pharmacology, Boston University School of Medicine , 72 East Concord Street, Boston, Massachusetts 02118, United States.
authors.forename: Margarita A
authors.initials: MA
authors.lastname: Tararina
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Medical Research (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, BCC-582, La Jolla, California 92037, United States.
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
authors.affiliation: Program in Biomolecular Pharmacology, Boston University School of Medicine , 72 East Concord Street, Boston, Massachusetts 02118, United States.|Department of Chemistry, Boston University , 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States.
authors.forename: Karen N
authors.initials: KN
authors.lastname: Allen
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004138:Dinitrocresols / Q000737:chemistry / Q000378:metabolism; D005415:Flavins / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009538:Nicotine / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D016958:Pseudomonas putida / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D004138:Dinitrocresols; D005415:Flavins; C024132:4,6-dinitro-o-cresol; C008173:isoalloxazine; D009538:Nicotine; D010088:Oxidoreductases; D008995:Monoamine Oxidase