Differences in the interactions of liver alcohol dehydrogenases with probes binding into the substrate pocket.
The interactions of three groups of probes (berberine alkaloids, tricyclic psychopharmaca and acridine derivatives) with isoenzymes of horse liver alcohol dehydrogenase and with rat liver alcohol dehydrogenase have been examined. These compounds inhibit the activity of the EE isoenzyme of horse liver alcohol dehydrogenase but differ in their behaviour towards the steroid-active enzymes (i.e. the ES isoenzyme of horse liver alcohol dehydrognase and alcohol dehydrogenase from rat liver): psychopharmaca inhibit, acridines activate and berberines do not bind. The ligands differ also in their influence on the modification of the EE isoenzyme by iodoacetate. Polarities (expressed as Kosower's Z values) of the respective binding sites on the EE isoenzyme were estimated from optical properties of bound probes. Berberines bind into a very hydrophobic area of the enzyme molecule, the binding site for psychopharmaca is moderately hydrophobic and that for acridines is rather polar. Steric arrangements of the binding sites are also discussed. The data presented confirm the existence of three distinct binding sites for these ligands in the substrate pocket of liver alcohol dehydrogenase.
D000166:Acridines / Q000494:pharmacology; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D006736:Horses; D007461:Iodoacetates / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008099:Liver / Q000201:enzymology*; D011485:Protein Binding; D051381:Rats; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity
D000166:Acridines; D000470:Alkaloids; D007461:Iodoacetates; D007527:Isoenzymes; D008024:Ligands; D000429:Alcohol Oxidoreductases