3LKZ: Structural And Functional Analyses Of A Conserved Hydrophobic Pocket Of Flavivirus Methyltransferase

Citation:
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-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.
PDB ID: 3LKZDownload
MMDB ID: 83826
PDB Deposition Date: 2010/1/28
Updated in MMDB: 2010/08
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 3LKZ: monomeric; determined by software (PISA)
Molecular Components in 3LKZ
Label Count Molecule
Protein (1 molecule)
1
Non-structural Protein 5
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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