Construction of a Model of the Candida Albicans Lanosterol 14-alpha-demethylase Active Site Using the Homology Modelling Technique

Pharm Acta Helv. 1998 Jan;72(5):271-7. doi: 10.1016/s0031-6865(97)00036-8.

Abstract

On the basis of all hitherto known P450 X-ray structures and applying standard homology modelling procedures a three-dimensional model of the lanosterol-14 alpha-demethylase active site was constructed. The modelled active site nicely hosts the natural substrate lanosterol and the substrate-enzyme complex displayed stability in a 70 ps molecular dynamics simulation. The importance of Thr 122 of lanosterol 14 alpha-demethylase for hydrogen bond formation with the 3-hydroxyl group of lanosterol was found to be a characteristic feature of the interaction geometry.

MeSH terms

  • Binding Sites
  • Candida albicans / enzymology*
  • Cytochrome P-450 Enzyme System / chemistry*
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Oxidoreductases / chemistry*
  • Protein Structure, Secondary
  • Sequence Homology, Amino Acid*
  • Sterol 14-Demethylase

Substances

  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • Sterol 14-Demethylase