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| - | [[Image:2oy0.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2oy0| PDB=2oy0 | SCENE= }} | | {{STRUCTURE_2oy0| PDB=2oy0 | SCENE= }} |
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| - | '''Crystal structure of the West Nile virus methyltransferase'''
| + | ===Crystal structure of the West Nile virus methyltransferase=== |
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| - | ==Overview==
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| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_17267492}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17267492 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17267492}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: N-7]] | | [[Category: N-7]] |
| | [[Category: Wnv]] | | [[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 Mon Jul 28 04:02:41 2008'' |
Revision as of 01:02, 28 July 2008
Template:STRUCTURE 2oy0
Crystal structure of the West Nile virus methyltransferase
Template:ABSTRACT PUBMED 17267492
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 Mon Jul 28 04:02:41 2008
