Cellular and Molecular Life Sciences

, Volume 67, Issue 17, pp 3005–3015 | Cite as

Enrichment of ligands with molecular dockings and subsequent characterization for human alcohol dehydrogenase 3

  • Mikko Hellgren
  • Jonas Carlsson
  • Linus J. Östberg
  • Claudia A. Staab
  • Bengt Persson
  • Jan-Olov Höög
Research Article


Alcohol dehydrogenase 3 (ADH3) has been assigned a role in nitric oxide homeostasis due to its function as an S-nitrosoglutathione reductase. As altered S-nitrosoglutathione levels are often associated with disease, compounds that modulate ADH3 activity might be of therapeutic interest. We performed a virtual screening with molecular dockings of more than 40,000 compounds into the active site of human ADH3. A novel knowledge-based scoring method was used to rank compounds, and several compounds that were not known to interact with ADH3 were tested in vitro. Two of these showed substrate activity (9-decen-1-ol and dodecyltetraglycol), where calculated binding scoring energies correlated well with the logarithm of the k cat/K m values for the substrates. Two compounds showed inhibition capacity (deoxycholic acid and doxorubicin), and with these data three different lines for specific inhibitors for ADH3 are suggested: fatty acids, glutathione analogs, and cholic acids.


Alcohol dehydrogenase Enzyme kinetics Inhibitors Molecular docking S-Nitrosoglutathione Virtual screening 



Alcohol dehydrogenase






Monte Carlo


Nitric oxide


Virtual screening


12-Hydroxydodecanoic acid



This work was supported by grants from Karolinska Institutet and Linköping University.


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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Mikko Hellgren
    • 1
  • Jonas Carlsson
    • 2
  • Linus J. Östberg
    • 1
  • Claudia A. Staab
    • 1
    • 4
  • Bengt Persson
    • 2
    • 3
  • Jan-Olov Höög
    • 1
  1. 1.Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSweden
  2. 2.IFM BioinformaticsLinköping UniversityLinköpingSweden
  3. 3.Department of Cell and Molecular BiologyKarolinska InstitutetStockholmSweden
  4. 4.Institute of Toxicology and Pharmacology for Natural ScientistsUniversity Medical School Schleswig-HolsteinKielGermany

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