Does molecular docking reveal alternative chemopreventive mechanism of activation of oxidoreductase by sulforaphane isothiocyanates?

J Mol Model. 2010 Jul;16(7):1205-12. doi: 10.1007/s00894-009-0628-5. Epub 2009 Dec 22.

Abstract

Isothiocyanates (ITC) are well-known chemopreventive agents extracted from vegetables. This activity results from the activation of human oxidoreductase. In this letter, the uncompetitive activatory mechanism of ITC was investigated using docking and molecular dynamics simulations. This indicates that NAD(P)H:quinone oxidoreductase can efficiently improve enzyme-substrate recognition within the catalytic site if the ITC activator supports the interaction in the uncompetitive binding site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Asparagine / chemistry
  • Asparagine / metabolism
  • Binding Sites
  • Catalytic Domain
  • Enzyme Activation
  • Humans
  • Isothiocyanates / chemistry*
  • Isothiocyanates / metabolism
  • Isothiocyanates / pharmacology
  • Models, Chemical
  • Models, Molecular*
  • Molecular Structure
  • NAD(P)H Dehydrogenase (Quinone) / chemistry*
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Substrate Specificity
  • Sulfoxides
  • Thiocyanates / chemistry
  • Thiocyanates / metabolism
  • Thiocyanates / pharmacology

Substances

  • Antineoplastic Agents
  • Isothiocyanates
  • Sulfoxides
  • Thiocyanates
  • Asparagine
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • sulforaphane