Oxidation of tetrahydro-beta-carboline by cytochrome P-450cam--determination and rationalisation of product distribution

Eur J Biochem. 1998 Jan 15;251(1-2):398-404. doi: 10.1046/j.1432-1327.1998.2510398.x.

Abstract

Cytochrome P-450cam oxidises 1,2,3,4-tetrahydro-beta-carboline, an indolic alkaloid. We report here measurements of the product distribution of this oxidation. To rationalise the experimental results, ab initio quantum-chemistry calculations of the product stabilities and molecular-dynamics calculations of the substrate-binding mode in the active site were performed. The calculations suggest that the product distribution is influenced by both the relative intrinsic gas-phase stabilities of the monohydroxy products and by conformational rearrangement of the active site on substrate binding.

MeSH terms

  • Binding Sites
  • Camphor 5-Monooxygenase / chemistry*
  • Camphor 5-Monooxygenase / metabolism*
  • Carbolines / chemistry
  • Carbolines / metabolism*
  • Cytochrome P-450 CYP1A1 / chemistry*
  • Cytochrome P-450 CYP1A1 / metabolism*
  • Mass Spectrometry / methods
  • Models, Molecular*
  • Oxidation-Reduction
  • Protein Conformation

Substances

  • Carbolines
  • tryptoline
  • Cytochrome P-450 CYP1A1
  • Camphor 5-Monooxygenase