Aldehyde Oxidases as Enzymes in Phase I Drug Metabolism

Cristiano Mota, Teresa Sacadura Santos-Silva, Mineko Terao, Enrico Garattini, Maria João Romão, Silke Leimkühler

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

This chapter discusses the significance of aldehyde oxidases for the design and development of new drugs, and discusses associated problems. Aldehyde oxidases are a group of enzymes with important functions in the context of drug and xenobiotic metabolism. Aldehyde oxidases (AOXs) and xanthine oxidoreductases (XORs) are structurally and evolutionarily linked molybdoflavoproteins. AOXs and XORs are widely distributed throughout all kingdoms of life, homologous proteins have been identified in many eukaryotic and prokaryotic organisms. The C-terminal domain III is binding the molybdenum cofactor (Moco) in its sulfido-containing form. At the catalytic site, the Moco adopts an approximately square pyramidal geometry. Heterologous expression systems for mammalian AOXs, including the human enzyme, in Escherichia coli have been developed, allowing site directed mutagenesis approaches to the role of distinct amino acid residues at the active site. The identification and characterization of genetic variants of enzymes involved in drug metabolism is highly relevant for the definition of the effectiveness and toxicity of pharmaceutical treatments.
Original languageEnglish
Title of host publicationPharmaceutical Biocatalysis: Fundamentals, Enzyme Inhibitors, and Enzymes in Health and Diseases
EditorsPeter Grunwald
PublisherRoutledge Taylor & Francis Group
Chapter13
Number of pages27
ISBN (Print)9780429295034
DOIs
Publication statusPublished - 27 Jun 2019

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    Mota, C., Santos-Silva, T. S., Terao, M., Garattini, E., Romão, M. J., & Leimkühler, S. (2019). Aldehyde Oxidases as Enzymes in Phase I Drug Metabolism. In P. Grunwald (Ed.), Pharmaceutical Biocatalysis: Fundamentals, Enzyme Inhibitors, and Enzymes in Health and Diseases Routledge Taylor & Francis Group. https://doi.org/10.1201/9780429295034-13