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

Int J Mol Sci. 2012;13(5):5375-405. doi: 10.3390/ijms13055375. Epub 2012 May 3.

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 O(2) to H(2)O(2). 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.

Keywords: amine oxidase; biogenesis; catalysis; cofactor; copper; protein crystallography.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amine Oxidase (Copper-Containing) / chemistry*
  • Amine Oxidase (Copper-Containing) / metabolism*
  • Animals
  • Coenzymes / chemistry
  • Coenzymes / metabolism
  • Crystallography, X-Ray / methods*
  • Dihydroxyphenylalanine / analogs & derivatives
  • Dihydroxyphenylalanine / chemistry
  • Dihydroxyphenylalanine / metabolism
  • Humans
  • Models, Molecular
  • Protein Biosynthesis
  • Protein Conformation
  • Protein Processing, Post-Translational

Substances

  • 2,4,5-trihydroxyphenylalanine quinone
  • Coenzymes
  • Dihydroxyphenylalanine
  • Amine Oxidase (Copper-Containing)