The first mammalian aldehyde oxidase crystal structure: Insights into substrate specificity

Catarina Coelho, Martin Mahro, José Trincão, Alexandra T P Carvalho, Maria João Ramos, Mineko Terao, Enrico Garattini, Silke Leimkühler, Maria João Romão

Research output: Contribution to journalArticle

Abstract

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 2.9A? . This is the first mammalian AOX whose structure has been solved. The structureprovidesimportantinsightsintotheproteinactivecenter and further evidence on the catalytic differences characterizing AOXand 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.

Original languageEnglish
Pages (from-to)40690-40702
Number of pages13
JournalJournal of Biological Chemistry
Volume287
Issue number48
DOIs
Publication statusPublished - Nov 23 2012

Fingerprint

Aldehyde Oxidase
Substrate Specificity
Crystal structure
Substrates
Xanthine Dehydrogenase
Proteins
Flavin-Adenine Dinucleotide
Molybdenum
Xanthine Oxidase
Liver
Xenobiotics
Molecular Dynamics Simulation
Aldehydes
Mutagenesis
Oxidation-Reduction
Catalytic Domain
Metabolism
Enzymes
Molecular dynamics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Coelho, C., Mahro, M., Trincão, J., Carvalho, A. T. P., Ramos, M. J., Terao, M., ... Romão, M. J. (2012). The first mammalian aldehyde oxidase crystal structure: Insights into substrate specificity. Journal of Biological Chemistry, 287(48), 40690-40702. https://doi.org/10.1074/jbc.M112.390419

The first mammalian aldehyde oxidase crystal structure : Insights into substrate specificity. / Coelho, Catarina; Mahro, Martin; Trincão, José; Carvalho, Alexandra T P; Ramos, Maria João; Terao, Mineko; Garattini, Enrico; Leimkühler, Silke; Romão, Maria João.

In: Journal of Biological Chemistry, Vol. 287, No. 48, 23.11.2012, p. 40690-40702.

Research output: Contribution to journalArticle

Coelho, C, Mahro, M, Trincão, J, Carvalho, ATP, Ramos, MJ, Terao, M, Garattini, E, Leimkühler, S & Romão, MJ 2012, 'The first mammalian aldehyde oxidase crystal structure: Insights into substrate specificity', Journal of Biological Chemistry, vol. 287, no. 48, pp. 40690-40702. https://doi.org/10.1074/jbc.M112.390419
Coelho, Catarina ; Mahro, Martin ; Trincão, José ; Carvalho, Alexandra T P ; Ramos, Maria João ; Terao, Mineko ; Garattini, Enrico ; Leimkühler, Silke ; Romão, Maria João. / The first mammalian aldehyde oxidase crystal structure : Insights into substrate specificity. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 48. pp. 40690-40702.
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