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

FEBS Letters

Moreno, Alberto¹  Parés, Xavier²  Persson, Bengt¹  Farrés, Jaume²  Jörnvall, Hans¹ 

[1] Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden;Department of Biochemistry and Molecular Biology, Universitat Autónoma de Barcelona, E-08193 Bellaterra (Barcelona), Spain

关键词: Alcohol dehydrogenase;    Class specificity;    Molecular modeling;    Structural comparison;    Substrate docking;   

DOI  :  10.1016/0014-5793(96)01009-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown