Kovár J, Dürrová E, Skurský L
Eur J Biochem. 1979 Nov;101(2):507-14. doi: 10.1111/j.1432-1033.1979.tb19745.x.
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.
研究了三组探针（小檗碱生物碱、三环类精神药物和吖啶衍生物）与马肝醇脱氢酶同工酶以及大鼠肝醇脱氢酶之间的相互作用。这些化合物抑制马肝醇脱氢酶EE同工酶的活性，但它们对具有甾体活性的酶（即马肝醇脱氢酶的ES同工酶和大鼠肝醇脱氢酶）的作用有所不同：精神药物起抑制作用，吖啶起激活作用，而小檗碱不结合。这些配体对碘乙酸对EE同工酶的修饰作用的影响也有所不同。根据结合探针的光学性质估算了EE同工酶上各个结合位点的极性（以科索尔Z值表示）。小檗碱结合到酶分子的一个非常疏水的区域，精神药物的结合位点具有中等疏水性，而吖啶的结合位点极性较强。还讨论了结合位点的空间排列。所提供的数据证实了在肝醇脱氢酶的底物口袋中存在这三种配体的三个不同结合位点。
