A three-dimensional model of the human class IV alcohol dehydrogenase has been calculated based upon the X-ray structure of the class I enzyme. As judged from the model, the substrate-binding site is wider than in class I, compatible with the differences in substrate specificities and the large difference in K,value for ethanol. Substrate docking performed for the class I structure and the class IV model show all-trans-retinol and 11-cis-retinol to bind better to tire class IV enzyme. The calculations also indicate that 16-hydroxyhexadecanoic acid binds in a different manner for the two enzyme classes. A simulation of coenzyme-binding indicates that the adenine ring of the coenzyme might be differently bound in class IV than in class I, decreasing the interactions with Asp-223 which is compatible with the higher k(cat) values for class IV.
|Publication status||Published - 21 Oct 1996|
- Alcohol dehydrogenase
- Class specificity
- Molecular modeling
- Structural comparison
- Substrate docking
Moreno, A., Farrés, J., Parés, X., Jörnvall, H., & Persson, B. (1996). Molecular modelling of human gastric alcohol dehydrogenase (class IV) and substrate docking: Differences towards the classical liver enzyme (class I). FEBS Letters, 395, 99-102. https://doi.org/10.1016/0014-5793(96)01009-5