Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The flavivirus methyltransferase (MTase) sequentially methylates the N7 and 2'-O positions of the viral RNA cap (GpppA-RNA --> m(7)GpppA-RNA --> m(7)GpppAm-RNA), using S-adenosyl-l-methionine (AdoMet) as a methyl donor. We report here that sinefungin (SIN), an AdoMet analog, inhibits several flaviviruses through suppression of viral MTase. The crystal structure of West Nile virus MTase in complex with SIN inhibitor at 2.0-A resolution revealed a flavivirus-conserved hydrophobic pocket located next to the AdoMet-binding site. The pocket is functionally critical in the viral replication and cap methylations. In addition, the N7 methylation efficiency was found to correlate with the viral replication ability. Thus, SIN analogs with modifications that interact with the hydrophobic pocket are potential specific inhibitors of flavivirus MTase.
Structural and functional analyses of a conserved hydrophobic pocket of flavivirus methyltransferase.,Dong H, Liu L, Zou G, Zhao Y, Li Z, Lim SP, Shi PY, Li H J Biol Chem. 2010 Oct 15;285(42):32586-95. Epub 2010 Aug 4. PMID:20685660[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dong H, Liu L, Zou G, Zhao Y, Li Z, Lim SP, Shi PY, Li H. Structural and functional analyses of a conserved hydrophobic pocket of flavivirus methyltransferase. J Biol Chem. 2010 Oct 15;285(42):32586-95. Epub 2010 Aug 4. PMID:20685660 doi:10.1074/jbc.M110.129197
