The First Mammalian Aldehyde Oxidase Crystal Structure INSIGHTS INTO SUBSTRATE SPECIFICITY

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Catarina Coelho (Author) Other; Martin Mahro (Author) Other; Jose Trincao (Author) Other; Alexandra T P Carvalho (Author) Other; Maria Joao Ramos (Author) FCUP; Mineko Terao (Author) Other; Enrico Garattini (Author) Other; Silke Leimkuehler (Author) Other; Maria Joao Romao (Author) Other

Journal

Title: Journal of Biological Chemistry

Vol. 287

Pages: 40690-40702

ISSN: 0021-9258

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 70 Citations

Scopus - 74 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-002-3AN

DOI: 10.1074/jbc.m112.390419

Abstract (EN): Aldehyde oxidases (AOXs) are homodimeric proteins belonging to the xanthine oxidase family of molybdenum-containing enzymes. Each 150-kDa monomer contains a FAD redox cofactor, two spectroscopically distinct [2Fe-2S] clusters, and a molybdenum cofactor located within the protein active site. AOXs are characterized by broad range substrate specificity, oxidizing different aldehydes and aromatic N-heterocycles. Despite increasing recognition of its role in the metabolism of drugs and xenobiotics, the physiological function of the protein is still largely unknown. We have crystallized and solved the crystal structure of mouse liver aldehyde oxidase 3 to 2.9 angstrom. This is the first mammalian AOX whose structure has been solved. The structure provides important insights into the protein active center and further evidence on the catalytic differences characterizing AOX and xanthine oxidoreductase. The mouse liver aldehyde oxidase 3 three-dimensional structure combined with kinetic, mutagenesis data, molecular docking, and molecular dynamics studies make a decisive contribution to understand the molecular basis of its rather broad substrate specificity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13