ArticleAntiviral research2014
Crystal structure of dengue virus methyltransferase without S-adenosyl-L-methionine.
Article in Antiviral research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 32 citations in OpenAlex.
- Virtual reality and cheminformatics-driven discovery of a potential broad-spectrum natural antagonist against flaviviral methyltransferases and its cytotoxicity evaluation.Journal of computer-aided molecular design · 2025Article
- Structural basis for broad-spectrum binding of AT-9010 to flaviviral methyltransferases.Archives of virology · 2025Article
- A Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection.Viruses · 2025Review
- Development in the Inhibition of Dengue Proteases as Drug Targets.Current medicinal chemistry · 2024Review
- Structural and functional basis of low-affinity SAM/SAH-binding in the conserved MTase of the multi-segmented Alongshan virus distantly related to canonical unsegmented flaviviruses.PLoS pathogens · 2023Article
- Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview.Microorganisms · 2023Review
- Article
- Current Trends and Limitations in Dengue Antiviral Research.Tropical medicine and infectious disease · 2021Review
- Flavivirus: From Structure to Therapeutics Development.Life (Basel, Switzerland) · 2021Review
- Natural Products with Potential to Treat RNA Virus Pathogens Including SARS-CoV-2.Journal of natural products · 2021Review
- How Diverse Are the Protein-Bound Conformations of Small-Molecule Drugs and Cofactors?Frontiers in chemistry · 2018Article
- An In-Silico Investigation of Phytochemicals as Antiviral Agents Against Dengue Fever.Combinatorial chemistry & high throughput screening · 2016Article
- Identification and Characterization of Novel Broad-Spectrum Inhibitors of the Flavivirus Methyltransferase.ACS infectious diseases · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Flavivirus methyltransferase is a genetically-validated antiviral target. Crystal structures of almost all available flavivirus methyltransferases contain S-adenosyl-L-methionine (SAM), the methyl donor molecule that co-purifies with the enzymes. This raises a possibility that SAM is an integral structural component required for the folding of dengue virus (DENV) methyltransferase. Here we exclude this possibility by solving the crystal structure of DENV methyltransferase without SAM. The SAM ligand was removed from the enzyme through a urea-mediated denaturation-and-renaturation protocol. The crystal structure of the SAM-depleted enzyme exhibits a vacant SAM-binding pocket, with a conformation identical to that of the SAM-enzyme co-crystal structure. Functionally, equivalent enzymatic activities (N-7 methylation, 2'-O methylation, and GMP-enzyme complex formation) were detected for the SAM-depleted and SAM-containing recombinant proteins. These results clearly indicate that the SAM molecule is not an essential component for the correct folding of DENV methyltransferase. Furthermore, the results imply a potential antiviral approach to search for inhibitors that can bind to the SAM-binding pocket and compete against SAM binding. To demonstrate this potential, we have soaked crystals of DENV methyltransferase without a bound SAM with the natural product Sinefungin and show that preformed crystals are capable of binding ligands in this pocket.
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