title: Structural basis for the role of mammalian aldehyde oxidases in the metabolism of drugs and xenobiotics.
abstract: Aldehyde oxidases (AOXs) are molybdo-flavoenzymes characterized by broad substrate specificity, oxidizing aromatic/aliphatic aldehydes into the corresponding carboxylic acids and hydroxylating various heteroaromatic rings. Mammals are characterized by a complement of species-specific AOX isoenzymes, that varies from one in humans (AOX1) to four in rodents (AOX1, AOX2, AOX3 and AOX4). The physiological function of mammalian AOX isoenzymes is unknown, although human AOX1 is an emerging enzyme in phase-I drug metabolism. Indeed, the number of therapeutic molecules under development which act as AOX substrates is increasing. The recent crystallization and structure determination of human AOX1 as well as mouse AOX3 has brought new insights into the mechanisms underlying substrate/inhibitor binding as well as the catalytic activity of this class of enzymes.
authors.affiliation: UCIBIO-Requimte, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. Electronic address: mjr@fct.unl.pt.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Romão
authors.affiliation: UCIBIO-Requimte, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Coelho
authors.affiliation: UCIBIO-Requimte, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Santos-Silva
authors.affiliation: Department of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Foti
authors.affiliation: Laboratory of Molecular Biology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milano, Italy.
authors.forename: Mineko
authors.initials: M
authors.lastname: Terao
authors.affiliation: Laboratory of Molecular Biology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milano, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Garattini
authors.affiliation: Department of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany. Electronic address: sleim@uni-potsdam.de.
authors.forename: Silke
authors.initials: S
authors.lastname: Leimkühler
mesh_terms: D042931:Aldehyde Oxidase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008322:Mammals; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D042931:Aldehyde Oxidase