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PDBsum entry 2pxc
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Transferase PDB id
2pxc

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
263 a.a. *
Ligands
SAM
G3A ×2
Waters ×24
* Residue conservation analysis
PDB id:
2pxc
Name: Transferase
Title: Crystal structure of the murray valley encephalitis virus ns5 2'-o methyltransferase domain in complex with sam and gtpa
Structure: Genome polyprotein [contains: capsid protein c (core protein). Envelope protein m (matrix protein). Major envelope protein e. Non-structural protein 1 (ns1). Non-structural protein 2a (ns2a). Flavivirin protease ns2b regulatory subunit. Flavivirin protease ns3 catalytic subunit. Non-structural protein 4a (ns4a). Non-structural protein 4b (ns4b). RNA-directed RNA polymerase (ec 2.7.7.48) (ns5)]. Chain: a. Fragment: ns5 2'-o methyltransferase domain: residues 2530-2798. Engineered: yes
Source: Murray valley encephalitis virus (strain mve-1- 51). Organism_taxid: 301478. Strain: mve-1-51, mvev. Gene: ns5. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.80Å     R-factor:   0.205     R-free:   0.256
Authors: R.Assenberg,J.Ren,A.Verma,T.S.Walter,D.Alderton,R.J.Hurrelbrink, S.D.Fuller,R.J.Owens,D.I.Stuart,J.M.Grimes,Oxford Protein Production Facility (Oppf)
Key ref: R.Assenberg et al. (2007). Crystal structure of the Murray Valley encephalitis virus NS5 methyltransferase domain in complex with cap analogues. J Gen Virol, 88, 2228-2236. PubMed id: 17622627
Date:
14-May-07     Release date:   29-May-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P05769  (POLG_MVEV5) -  Genome polyprotein from Murray valley encephalitis virus (strain MVE-1-51)
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		3434 a.a.
263 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.2.1.1.56  - mRNA (guanine-N(7))-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L- methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-homocysteine
5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA
 +
S-adenosyl-L- methionine
Bound ligand (Het Group name = SAM)
corresponds exactly 		= 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA
 + S-adenosyl-L-homocysteine
   Enzyme class 2: E.C.2.1.1.57  - methyltransferase cap1.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)- (2'-O-methyl-ribonucleoside) in mRNA + S-adenosyl-L-homocysteine + H+
5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA
 +
S-adenosyl-L-methionine
Bound ligand (Het Group name = SAM)
corresponds exactly 		= 5'-end (N(7)-methyl 5'-triphosphoguanosine)- (2'-O-methyl-ribonucleoside) in mRNA
 + S-adenosyl-L-homocysteine
 + H(+)
   Enzyme class 3: E.C.2.7.7.48  - RNA-directed Rna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
RNA(n)
 + ribonucleoside 5'-triphosphate
 = RNA(n+1)
 + diphosphate
   Enzyme class 4: E.C.3.4.21.91  - flavivirin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Selective hydrolysis of Xaa-Xaa-|-Xbb bonds in which each of the Xaa can be either Arg or Lys and Xbb can be either Ser or Ala.
   Enzyme class 5: E.C.3.6.1.15  - nucleoside-triphosphate phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H+
ribonucleoside 5'-triphosphate
 + H2O
 = ribonucleoside 5'-diphosphate
 + phosphate
 + H(+)
   Enzyme class 6: E.C.3.6.4.13  - Rna helicase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate + H+
ATP
Bound ligand (Het Group name = G3A)
matches with 62.00% similarity 		+ H2O
 = ADP
 + phosphate
 + H(+)
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
J Gen Virol 88:2228-2236 (2007)
PubMed id: 17622627  
 
 
Crystal structure of the Murray Valley encephalitis virus NS5 methyltransferase domain in complex with cap analogues.
R.Assenberg, J.Ren, A.Verma, T.S.Walter, D.Alderton, R.J.Hurrelbrink, S.D.Fuller, S.Bressanelli, R.J.Owens, D.I.Stuart, J.M.Grimes.
 
  ABSTRACT  
 
We have determined the high resolution crystal structure of the methyltransferase domain of the NS5 polypeptide from the Murray Valley encephalitis virus. This domain is unusual in having both the N7 and 2'-O methyltransferase activity required for Cap 1 synthesis. We have also determined structures for complexes of this domain with nucleotides and cap analogues providing information on cap binding, based on which we suggest a model of how the sequential methylation of the N7 and 2'-O groups of the cap may be coordinated.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19776234 B.Selisko, F.F.Peyrane, B.Canard, K.Alvarez, and E.Decroly (2010).
Biochemical characterization of the (nucleoside-2'O)-methyltransferase activity of dengue virus protein NS5 using purified capped RNA oligonucleotides (7Me)GpppAC(n) and GpppAC(n).
  J Gen Virol, 91, 112-121.  
  20862256 L.J.Yap, D.Luo, K.Y.Chung, S.P.Lim, C.Bodenreider, C.Noble, P.Y.Shi, and J.Lescar (2010).
Crystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric RNA.
  PLoS One, 5, 0.
PDB code: 2xbm
19622863 A.M.Jansson, E.Jakobsson, P.Johansson, V.Lantez, B.Coutard, X.de Lamballerie, T.Unge, and T.A.Jones (2009).
Structure of the methyltransferase domain from the Modoc virus, a flavivirus with no known vector.
  Acta Crystallogr D Biol Crystallogr, 65, 796-803.
PDB codes: 2wa1 2wa2
19101564 B.J.Geiss, A.A.Thompson, A.J.Andrews, R.L.Sons, H.H.Gari, S.M.Keenan, and O.B.Peersen (2009).
Analysis of flavivirus NS5 methyltransferase cap binding.
  J Mol Biol, 385, 1643-1654.
PDB codes: 3eva 3evb 3evc 3evd 3eve 3evf 3evg
19850911 M.Issur, B.J.Geiss, I.Bougie, F.Picard-Jean, S.Despins, J.Mayette, S.E.Hobdey, and M.Bisaillon (2009).
The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure.
  RNA, 15, 2340-2350.  
19793813 R.Assenberg, E.Mastrangelo, T.S.Walter, A.Verma, M.Milani, R.J.Owens, D.I.Stuart, J.M.Grimes, and E.J.Mancini (2009).
Crystal structure of a novel conformational state of the flavivirus NS3 protein: implications for polyprotein processing and viral replication.
  J Virol, 83, 12895-12906.
PDB code: 2wv9
18448528 B.Zhang, H.Dong, Y.Zhou, and P.Y.Shi (2008).
Genetic interactions among the West Nile virus methyltransferase, the RNA-dependent RNA polymerase, and the 5' stem-loop of genomic RNA.
  J Virol, 82, 7047-7058.  
18757072 D.Bhattacharya, S.Hoover, S.P.Falk, B.Weisblum, M.Vestling, and R.Striker (2008).
Phosphorylation of yellow fever virus NS5 alters methyltransferase activity.
  Virology, 380, 276-284.  
18305027 H.Dong, S.Ren, B.Zhang, Y.Zhou, F.Puig-Basagoiti, H.Li, and P.Y.Shi (2008).
West Nile virus methyltransferase catalyzes two methylations of the viral RNA cap through a substrate-repositioning mechanism.
  J Virol, 82, 4295-4307.  
18501946 H.Dong, S.Ren, H.Li, and P.Y.Shi (2008).
Separate molecules of West Nile virus methyltransferase can independently catalyze the N7 and 2'-O methylations of viral RNA cap.
  Virology, 377, 1-6.  
17989694 M.De la Peña, O.J.Kyrieleis, and S.Cusack (2007).
Structural insights into the mechanism and evolution of the vaccinia virus mRNA cap N7 methyl-transferase.
  EMBO J, 26, 4913-4925.
PDB code: 2vdw
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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