Abstract
| Original language | English |
|---|---|
| Title of host publication | Pharmaceutical Biocatalysis: Fundamentals, Enzyme Inhibitors, and Enzymes in Health and Diseases |
| Editors | Peter Grunwald |
| Publisher | Routledge Taylor & Francis Group |
| Chapter | 13 |
| Number of pages | 27 |
| ISBN (Print) | 9780429295034 |
| DOIs | |
| Publication status | Published - 27 Jun 2019 |
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Aldehyde Oxidases as Enzymes in Phase I Drug Metabolism. / Mota, Cristiano; Santos-Silva, Teresa Sacadura; Terao, Mineko; Garattini, Enrico; Romão, Maria João; Leimkühler, Silke.
Pharmaceutical Biocatalysis: Fundamentals, Enzyme Inhibitors, and Enzymes in Health and Diseases. ed. / Peter Grunwald. Routledge Taylor & Francis Group, 2019.Research output: Chapter in Book/Report/Conference proceeding › Chapter
TY - CHAP
T1 - Aldehyde Oxidases as Enzymes in Phase I Drug Metabolism
AU - Mota, Cristiano
AU - Santos-Silva, Teresa Sacadura
AU - Terao, Mineko
AU - Garattini, Enrico
AU - Romão, Maria João
AU - Leimkühler, Silke
PY - 2019/6/27
Y1 - 2019/6/27
N2 - 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.
AB - 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.
U2 - 10.1201/9780429295034-13
DO - 10.1201/9780429295034-13
M3 - Chapter
SN - 9780429295034
BT - Pharmaceutical Biocatalysis: Fundamentals, Enzyme Inhibitors, and Enzymes in Health and Diseases
A2 - Grunwald, Peter
PB - Routledge Taylor & Francis Group
ER -