ArticleJournal of chemical information and modeling2012
Unlocking the binding and reaction mechanism of hydroxyurea substrates as biological nitric oxide donors.
Article in Journal of chemical information and modeling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 19 citations in OpenAlex.
- Hydration ofMolecules (Basel, Switzerland) · 2024Article
- Oxidative pathways in the sickle cell and beyond.Blood cells, molecules & diseases · 2018Review
- Elucidating a chemical defense mechanism of Antarctic sponges: A computational study.Journal of molecular graphics & modelling · 2017Article
- Identification of Ecdysone Hormone Receptor Agonists as a Therapeutic Approach for Treating Filarial Infections.PLoS neglected tropical diseases · 2016Article
- ProBiS-CHARMMing: Web Interface for Prediction and Optimization of Ligands in Protein Binding Sites.Journal of chemical information and modeling · 2015Article
- How does catalase release nitric oxide? A computational structure-activity relationship study.Journal of chemical information and modeling · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Hydroxyurea is the only FDA approved treatment of sickle cell disease. It is believed that the primary mechanism of action is associated with the pharmacological elevation of nitric oxide in the blood; however, the exact details of this are still unclear. In the current work, we investigate the atomic level details of this process using a combination of flexible-ligand/flexible-receptor virtual screening coupled with energetic analysis that decomposes interaction energies. Utilizing these methods, we were able to elucidate the previously unknown substrate binding modes of a series of hydroxyurea analogs to hemoglobin and the concomitant structural changes of the enzyme. We identify a backbone carbonyl that forms a hydrogen bond with bound substrates. Our results are consistent with kinetic and electron paramagnetic resonance (EPR) measurements of hydroxyurea-hemoglobin reactions, and a full mechanism is proposed that offers new insights into possibly improving substrate binding and/or reactivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.