Crystallization and preliminary X-ray diffraction analysis of cytochrome P450sca-2 from Streptomyces carbophilus involved in production of pravastatin sodium, a tissue-selective inhibitor of HMG-CoA reductase

Acta Crystallogr D Biol Crystallogr. 1999 Jun;55(Pt 6):1209-11. doi: 10.1107/s0907444999003716.

Abstract

Cytochrome P450sca-2 from Streptomyces carbophilus catalyzes the hydroxylation of ML-236B sodium salt to pravastatin sodium, a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase. HMG-CoA reductase is a key enzyme in cholesterol biosynthesis. Crystals of the protein were obtained by the vapour-diffusion method, using ammonium sulfate as a precipitant. The crystals belong to the trigonal space group P3121 (or its enantiomorph, P3221) with unit-cell dimensions a = 103.5, c = 79.8 A. Assuming the presence of one molecule in the asymmetric unit, the calculated value of Vm is 2.68 A3 Da-1. A native data set was collected to a resolution of 2.2 A.

MeSH terms

  • Crystallization
  • Crystallography, X-Ray
  • Cytochrome P-450 Enzyme System / chemistry*
  • Cytochrome P-450 Enzyme System / isolation & purification
  • Cytochrome P-450 Enzyme System / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / metabolism*
  • Mixed Function Oxygenases / chemistry*
  • Mixed Function Oxygenases / isolation & purification
  • Mixed Function Oxygenases / metabolism
  • Pravastatin / biosynthesis*
  • Protein Conformation
  • Streptomyces / enzymology*
  • X-Ray Diffraction

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • mevastatin hydroxylase
  • Pravastatin