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Molecular modelling of human gastric alcohol dehydrogenase (class IV) and substrate docking: differences towards the classical liver enzyme (class I)
Author(s) -
Moreno Alberto,
Farrés Jaume,
Parés Xavier,
Jörnvall Hans,
Persson Bengt
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)01009-5
Subject(s) - alcohol dehydrogenase , docking (animal) , human liver , enzyme , chemistry , biochemistry , class (philosophy) , stereochemistry , computer science , medicine , artificial intelligence , nursing
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 m 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 the 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.