3LKZ
Structural and functional analyses of a conserved hydrophobic pocket of flavivirus methyltransferase
Summary for 3LKZ
| Entry DOI | 10.2210/pdb3lkz/pdb |
| Related | 2OY0 |
| Descriptor | Non-structural protein 5, SINEFUNGIN, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | west nile virus, flavivirus, methyltransferase, inhibitor, pocket, nucleotide-binding, rna replication, viral protein |
| Biological source | West Nile virus (WNV) |
| Cellular location | Envelope protein E: Virion membrane; Multi- pass membrane protein: Q9Q6P4 |
| Total number of polymer chains | 2 |
| Total formula weight | 74432.59 |
| Authors | |
| Primary citation | Dong, H.,Liu, L.,Zou, G.,Zhao, Y.,Li, Z.,Lim, S.P.,Shi, P.Y.,Li, H. Structural and functional analyses of a conserved hydrophobic pocket of flavivirus methyltransferase. J.Biol.Chem., 285:32586-32595, 2010 Cited by PubMed Abstract: 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-Å 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. PubMed: 20685660DOI: 10.1074/jbc.M110.129197 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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