Structural basis for the role of mammalian aldehyde oxidases in the metabolism of drugs and xenobiotics
- Citation:
- Romão, MJ, Coelho C, Santos-Silva T, Foti A, Terao M, Garattini E, Leimkühler S. 2017. Structural basis for the role of mammalian aldehyde oxidases in the metabolism of drugs and xenobiotics. Current Opinion in Chemical Biology. 37:39-47.
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.
Notes:
Biocatalysis & biotransformation * Bioinorganic Chemistry