Inhibition of nicotinoprotein (NAD+-containing) alcohol dehydrogenase by trans-4-(N,N-dimethylamino)-cinnamaldehyde binding to the active site.
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.
Piersma
Sander R
SR
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Norin
Annika
A
de Vries
Simon
S
Jörnvall
Hans
H
Duine
Johannis A
JA
D039903:Actinobacteria / Q000201:enzymology; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D002384:Catalysis; D002934:Cinnamates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D015032:Zinc / Q000378:metabolism
D002934:Cinnamates; C018523:4-dimethylaminocinnamaldehyde; D000426:Alcohol Dehydrogenase; D015032:Zinc