Title |
Enrichment of ligands with molecular dockings and subsequent characterization for human alcohol dehydrogenase 3
|
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Published in |
Cellular and Molecular Life Sciences, April 2010
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DOI | 10.1007/s00018-010-0370-2 |
Pubmed ID | |
Authors |
Mikko Hellgren, Jonas Carlsson, Linus J. Östberg, Claudia A. Staab, Bengt Persson, Jan-Olov Höög |
Abstract |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 6% |
Brazil | 1 | 6% |
Unknown | 15 | 88% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 7 | 41% |
Other | 2 | 12% |
Student > Master | 2 | 12% |
Student > Bachelor | 2 | 12% |
Student > Doctoral Student | 1 | 6% |
Other | 2 | 12% |
Unknown | 1 | 6% |
Readers by discipline | Count | As % |
---|---|---|
Chemistry | 5 | 29% |
Agricultural and Biological Sciences | 3 | 18% |
Biochemistry, Genetics and Molecular Biology | 2 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 6% |
Veterinary Science and Veterinary Medicine | 1 | 6% |
Other | 4 | 24% |
Unknown | 1 | 6% |