Molecular modelling of human gastric alcohol dehydrogenase (class IV) and substrate docking: Differences towards the classical liver enzyme (class I)

Alberto Moreno, Jaume Farrés, Xavier Parés, Hans Jörnvall, Bengt Persson

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23 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)99-102
JournalFEBS Letters
Volume395
DOIs
Publication statusPublished - 21 Oct 1996

Keywords

  • Alcohol dehydrogenase
  • Class specificity
  • Molecular modeling
  • Structural comparison
  • Substrate docking

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