The role of protein crystallography in defining the mechanisms of biogenesis and catalysis in copper amine oxidase

Valerie J. Klema, Carrie M. Wilmot

Research output: Contribution to journalReview article

21 Citations (Scopus)

Abstract

Copper amine oxidases (CAOs) are a ubiquitous group of enzymes that catalyze the conversion of primary amines to aldehydes coupled to the reduction of O2 to H2O2. These enzymes utilize a wide range of substrates from methylamine to polypeptides. Changes in CAO activity are correlated with a variety of human diseases, including diabetes mellitus, Alzheimer's disease, and inflammatory disorders. CAOs contain a cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), that is required for catalytic activity and synthesized through the post-translational modification of a tyrosine residue within the CAO polypeptide. TPQ generation is a self-processing event only requiring the addition of oxygen and Cu(II) to the apoCAO. Thus, the CAO active site supports two very different reactions: TPQ synthesis, and the two electron oxidation of primary amines. Crystal structures are available from bacterial through to human sources, and have given insight into substrate preference, stereospecificity, and structural changes during biogenesis and catalysis. In particular both these processes have been studied in crystallo through the addition of native substrates. These latter studies enable intermediates during physiological turnover to be directly visualized, and demonstrate the power of this relatively recent development in protein crystallography.

Original languageEnglish (US)
Pages (from-to)5375-5405
Number of pages31
JournalInternational Journal of Molecular Sciences
Volume13
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

Fingerprint

biological evolution
Amine Oxidase (Copper-Containing)
Crystallography
oxidase
Catalysis
crystallography
catalysis
Amines
amines
proteins
Proteins
Copper
copper
quinones
Polypeptides
Substrates
polypeptides
Bacterial Structures
enzymes
Peptides

Keywords

  • Amine oxidase
  • Biogenesis
  • Catalysis
  • Cofactor
  • Copper
  • Protein crystallography

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

The role of protein crystallography in defining the mechanisms of biogenesis and catalysis in copper amine oxidase. / Klema, Valerie J.; Wilmot, Carrie M.

In: International Journal of Molecular Sciences, Vol. 13, No. 5, 05.2012, p. 5375-5405.

Research output: Contribution to journalReview article

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