A Multiperspective Approach to Solvent Regulation of Enzymatic Activity: HMG-CoA Reductase

Chembiochem. 2018 Jan 18;19(2):153-158. doi: 10.1002/cbic.201700596. Epub 2017 Dec 21.

Abstract

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase was investigated in different organic cosolvents by means of kinetic and calorimetric measurements, molecular dynamics simulations, and small-angle X-ray scattering. The combined experimental and theoretical techniques were essential to complement each other's limitations in the investigation of the complex interaction pattern between the enzyme, different solvent types, and concentrations. In this way, the underlying mechanisms for the loss of enzyme activity in different water-miscible solvents could be elucidated. These include direct inhibitory effects onto the active center and structural distortions.

Keywords: differential scanning calorimetry; enzymes; molecular modeling; small-angle X-ray scattering; solvent effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetonitriles / chemistry
  • Acetonitriles / metabolism*
  • Acyl Coenzyme A / chemistry
  • Acyl Coenzyme A / metabolism*
  • Alcohols / chemistry
  • Alcohols / metabolism*
  • Calorimetry
  • Ionic Liquids / chemistry
  • Ionic Liquids / metabolism*
  • Kinetics
  • Molecular Dynamics Simulation
  • Scattering, Small Angle
  • Solvents / chemistry
  • Solvents / metabolism
  • Sulfolobus solfataricus / enzymology
  • X-Ray Diffraction

Substances

  • Acetonitriles
  • Acyl Coenzyme A
  • Alcohols
  • Ionic Liquids
  • Solvents
  • 3-hydroxy-3-methylglutaryldithio-coenzyme A
  • acetonitrile