Inhibition of Nicotinoprotein (NAD+-containing) Alcohol Dehydrogenase by trans-4-(N,N-dimethylamino)-cinnamaldehyde Binding to the Active Site

J Protein Chem. 2003 Jul;22(5):457-61. doi: 10.1023/b:jopc.0000005461.53788.ee.

Abstract

Ethanol oxidation by nicotinoprotein alcohol dehydrogenase (np-ADH) from the bacterium Amycolatopsis methanolica is inhibited by trans-4-(N,N-dimethylamino)-cinnamaldehyde through direct binding to the catalytic zinc ion in a substrate-like geometry. This binding is accompanied by a characteristic red shift of the aldehyde absorbance from 398 nm to 467 nm. Np-ADH is structurally related to mammalian ADH class I, and a model of np-ADH shows how the cinnamaldehyde derivative can be accommodated in the active site of the nicotinoprotein, correlating the structural and enzymological data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / enzymology
  • Alcohol Dehydrogenase / antagonists & inhibitors*
  • Alcohol Dehydrogenase / chemistry
  • Alcohol Dehydrogenase / metabolism*
  • Binding Sites / drug effects
  • Catalysis
  • Cinnamates / chemistry
  • Cinnamates / metabolism
  • Cinnamates / pharmacology*
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Zinc / metabolism

Substances

  • Cinnamates
  • 4-dimethylaminocinnamaldehyde
  • Alcohol Dehydrogenase
  • Zinc