2oy0
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2oy0.gif|left|200px]] | [[Image:2oy0.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2oy0", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | | | + | --> |
| - | + | {{STRUCTURE_2oy0| PDB=2oy0 | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal structure of the West Nile virus methyltransferase''' | '''Crystal structure of the West Nile virus methyltransferase''' | ||
| Line 30: | Line 27: | ||
[[Category: Zhao, Y W.]] | [[Category: Zhao, Y W.]] | ||
[[Category: 2'-o]] | [[Category: 2'-o]] | ||
| - | [[Category: | + | [[Category: Flavivirus]] |
| - | [[Category: | + | [[Category: Methyltransferase]] |
| - | [[Category: | + | [[Category: N-7]] |
| - | [[Category: | + | [[Category: Wnv]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 11:54:36 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 08:54, 4 May 2008
Crystal structure of the West Nile virus methyltransferase
Overview
The plus-strand RNA genome of flavivirus contains a 5' terminal cap 1 structure (m7GpppAmG). The flaviviruses encode one methyltransferase, located at the N-terminal portion of the NS5 protein, to catalyze both guanine N-7 and ribose 2'-OH methylations during viral cap formation. Representative flavivirus methyltransferases from dengue, yellow fever, and West Nile virus (WNV) sequentially generate GpppA-->m7GpppA-->m7GpppAm. The 2'-O methylation can be uncoupled from the N-7 methylation, since m7GpppA-RNA can be readily methylated to m7GpppAm-RNA. Despite exhibiting two distinct methylation activities, the crystal structure of WNV methyltransferase at 2.8 A resolution showed a single binding site for S-adenosyl-L-methionine (SAM), the methyl donor. Therefore, substrate GpppA-RNA should be repositioned to accept the N-7 and 2'-O methyl groups from SAM during the sequential reactions. Electrostatic analysis of the WNV methyltransferase structure showed that, adjacent to the SAM-binding pocket, is a highly positively charged surface that could serve as an RNA binding site during cap methylations. Biochemical and mutagenesis analyses show that the N-7 and 2'-O cap methylations require distinct buffer conditions and different side chains within the K61-D146-K182-E218 motif, suggesting that the two reactions use different mechanisms. In the context of complete virus, defects in both methylations are lethal to WNV; however, viruses defective solely in 2'-O methylation are attenuated and can protect mice from later wild-type WNV challenge. The results demonstrate that the N-7 methylation activity is essential for the WNV life cycle and, thus, methyltransferase represents a novel target for flavivirus therapy.
About this Structure
2OY0 is a Single protein structure of sequence from West nile virus. Full crystallographic information is available from OCA.
Reference
Structure and function of flavivirus NS5 methyltransferase., Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H, J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 Page seeded by OCA on Sun May 4 11:54:36 2008
Categories: Single protein | West nile virus | Guo, Y. | Li, H M. | Shi,P Y. | Zhao, Y W. | 2'-o | Flavivirus | Methyltransferase | N-7 | Wnv
