Enrichment of ligands with molecular dockings and subsequent characterization for human alcohol dehydrogenase 3
2010 (English)In: CELLULAR AND MOLECULAR LIFE SCIENCES, ISSN 1420-682X, Vol. 67, no 17, 3005-3015 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Springer Science Business Media , 2010. Vol. 67, no 17, 3005-3015 p.
Alcohol dehydrogenase, Enzyme kinetics, Inhibitors, Molecular docking, S-Nitrosoglutathione, Virtual screening
Engineering and Technology
IdentifiersURN: urn:nbn:se:liu:diva-58964DOI: 10.1007/s00018-010-0370-2ISI: 000280917900011OAI: oai:DiVA.org:liu-58964DiVA: diva2:347773