PDBsum entry 1vpt

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Methyltransferase PDB id
Jmol PyMol
Protein chain
291 a.a. *
Waters ×203
* Residue conservation analysis
PDB id:
Name: Methyltransferase
Title: As11 variant of vaccinia virus protein vp39 in complex with adenosyl-l-methionine
Structure: Vp39. Chain: a. Synonym: poly(a) polymerase regulatory subunit. Engineered: yes. Mutation: yes
Source: Vaccinia virus. Organism_taxid: 10254. Strain: wr. Expressed in: escherichia coli. Expression_system_taxid: 562
1.80Å     R-factor:   0.215     R-free:   0.250
Authors: A.E.Hodel,P.D.Gershon,X.Shi,F.A.Quiocho
Key ref:
A.E.Hodel et al. (1996). The 1.85 A structure of vaccinia protein VP39: a bifunctional enzyme that participates in the modification of both mRNA ends. Cell, 85, 247-256. PubMed id: 8612277 DOI: 10.1016/S0092-8674(00)81101-0
20-Mar-96     Release date:   17-Aug-96    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P07617  (MCE_VACCW) -  Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase
333 a.a.
291 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Methyltransferase cap1.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-adenosyl-L-methionine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)- (purine-ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N(7)- methyl 5'-triphosphoguanosine)-(2'-O-methyl-purine-ribonucleotide)- [mRNA]
Bound ligand (Het Group name = SAM)
corresponds exactly
+ 5'-(N(7)-methyl 5'-triphosphoguanosine)- (purine-ribonucleotide)-[mRNA]
= S-adenosyl-L-homocysteine
+ 5'-(N(7)- methyl 5'-triphosphoguanosine)-(2'-O-methyl-purine-ribonucleotide)- [mRNA]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     virion   1 term 
  Biological process     methylation   8 terms 
  Biochemical function     transferase activity     5 terms  


    Added reference    
DOI no: 10.1016/S0092-8674(00)81101-0 Cell 85:247-256 (1996)
PubMed id: 8612277  
The 1.85 A structure of vaccinia protein VP39: a bifunctional enzyme that participates in the modification of both mRNA ends.
A.E.Hodel, P.D.Gershon, X.Shi, F.A.Quiocho.
VP39 is a bifunctional vaccinia virus protein that acts as both an mRNA cap-specific RNA 2'-O-methyltransferase and a poly(A) polymerase processivity factor. Here, we report the 1.85 A crystal structure of a VP39 variant complexed with its AdoMet cofactor. VP39 comprises a single core domain with structural similarity to the catalytic domains of other methyltransferases. Surface features and mutagenesis data suggest two possible RNA-binding sites with novel underlying architecture, one of which forms a cleft spanning the region adjacent to the methyltransferase active site. This report provides a prototypic structure for an RNA methyltransferase, a protein that interacts with the mRNA 5' cap, and an intact poxvirus protein.
  Selected figure(s)  
Figure 4.
Figure 4. Stereo Diagram Showing Electron Density at the AdoMet-Binding Site and the Interactions between AdoMet and Nearby Residues of AS11The F[o]-F[c] electron density map, contoured at 2.5 σ, was calculated at 1.85 Å from a model that did not contain the AdoMet molecule. As shown, the AdoMet molecule is clearly defined including its donor methyl group. Residues appropriately positioned to make either hydrogen bonding or van der Waals contact with AdoMet are shown. Carbon atoms/bonds are colored gray/white; sulfur, yellow; nitrogen, blue; and oxygen, red. The 13 potential hydrogen bonds whose lengths were in the range 2.5–3.3 Å are represented by dashed green lines. For clarity, G68 (whose backbone carbonyl oxygen forms the near vertical hydrogen bond with the α-ammonium group of the AdoMet methionine moiety) is not labeled. One of the three potential hydrogen bonds to the 3′ OH of the AdoMet ribose is almost completely hidden in the view shown.
Figure 5.
Figure 5. Schematic Showing a Model for the Binding of a 5′-Capped RNA Strand to the Cleft and Methyltransferase Active SiteThe cleft is viewed from an angle similar to that in Figure 3A, Figure 3D, and 3G. Important regions of the surface are labeled, including the putative binding site for the terminal (m^7G) nucleotide of cap 0 (cap binding); the position at which the donor methyl of AdoMet protrudes into the cleft (donor methyl); the active site and associated basic region (basic region/active site); the missing 142–147 loop (which contains basic side chains in wild-type VP39) and the hydrophobic pocket at the distal end of the cleft. RNA nucleotides are represented by dark ovals. An internucleotide spacing of vert, similar 5 Å per base was used, based upon the spacing determined for single-stranded DNA bound to gp32 (in which DNA bases were unstacked; [44]).
  The above figures are reprinted by permission from Cell Press: Cell (1996, 85, 247-256) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22138959 E.Decroly, F.Ferron, J.Lescar, and B.Canard (2012).
Conventional and unconventional mechanisms for capping viral mRNA.
  Nat Rev Microbiol, 10, 51-65.  
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.  
19622863 A.M.Jansson, E.Jakobsson, P.Johansson, V.Lantez, B.Coutard, 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
19946139 K.Van Vliet, M.R.Mohamed, L.Zhang, N.Y.Villa, S.J.Werden, J.Liu, and G.McFadden (2009).
Poxvirus proteomics and virus-host protein interactions.
  Microbiol Mol Biol Rev, 73, 730-749.  
18048356 B.Mittra, J.R.Zamudio, J.M.Bujnicki, J.Stepinski, E.Darzynkiewicz, D.A.Campbell, and N.R.Sturm (2008).
The TbMTr1 Spliced Leader RNA Cap 1 2 '-O-Ribose Methyltransferase from Trypanosoma brucei Acts with Substrate Specificity.
  J Biol Chem, 283, 3161-3172.  
18417574 E.Decroly, I.Imbert, B.Coutard, M.Bouvet, B.Selisko, K.Alvarez, A.E.Gorbalenya, E.J.Snijder, and B.Canard (2008).
Coronavirus nonstructural protein 16 is a cap-0 binding enzyme possessing (nucleoside-2'O)-methyltransferase activity.
  J Virol, 82, 8071-8084.  
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.  
18367228 M.N.Becker, T.M.Todd, and R.W.Moyer (2008).
An Amsacta moorei entomopoxvirus ortholog of the poly(A) polymerase small subunit exhibits methyltransferase activity and is non-essential for virus growth.
  Virology, 375, 624-636.  
18848710 S.E.Galloway, P.E.Richardson, and G.W.Wertz (2008).
Analysis of a structural homology model of the 2'-O-ribose methyltransferase domain within the vesicular stomatitis virus L protein.
  Virology, 382, 69-82.  
18385232 Y.Li, and L.A.Guarino (2008).
Roles of LEF-4 and PTP/BVP RNA triphosphatases in processing of baculovirus late mRNAs.
  J Virol, 82, 5573-5583.  
17473012 E.Mastrangelo, M.Bollati, M.Milani, B.Selisko, F.Peyrane, B.Canard, G.Grard, Lamballerie, and M.Bolognesi (2007).
Structural bases for substrate recognition and activity in Meaban virus nucleoside-2'-O-methyltransferase.
  Protein Sci, 16, 1133-1145.
PDB code: 2oxt
17267492 Y.Zhou, D.Ray, Y.Zhao, H.Dong, S.Ren, Z.Li, Y.Guo, K.A.Bernard, P.Y.Shi, and H.Li (2007).
Structure and function of flavivirus NS5 methyltransferase.
  J Virol, 81, 3891-3903.
PDB code: 2oy0
16912287 D.Ray, A.Shah, M.Tilgner, Y.Guo, Y.Zhao, H.Dong, T.S.Deas, Y.Zhou, H.Li, and P.Y.Shi (2006).
West Nile virus 5'-cap structure is formed by sequential guanine N-7 and ribose 2'-O methylations by nonstructural protein 5.
  J Virol, 80, 8362-8370.  
16301606 G.K.Arhin, H.Li, E.Ullu, and C.Tschudi (2006).
A protein related to the vaccinia virus cap-specific methyltransferase VP39 is involved in cap 4 modification in Trypanosoma brucei.
  RNA, 12, 53-62.  
16709677 J.Li, J.T.Wang, and S.P.Whelan (2006).
A unique strategy for mRNA cap methylation used by vesicular stomatitis virus.
  Proc Natl Acad Sci U S A, 103, 8493-8498.  
16757738 J.R.Zamudio, B.Mittra, G.M.Zeiner, M.Feder, J.M.Bujnicki, N.R.Sturm, and D.A.Campbell (2006).
Complete cap 4 formation is not required for viability in Trypanosoma brucei.
  Eukaryot Cell, 5, 905-915.  
17028101 M.P.Hall, and C.K.Ho (2006).
Functional characterization of a 48 kDa Trypanosoma brucei cap 2 RNA methyltransferase.
  Nucleic Acids Res, 34, 5594-5602.  
15811913 A.Alexandrov, E.J.Grayhack, and E.M.Phizicky (2005).
tRNA m7G methyltransferase Trm8p/Trm82p: evidence linking activity to a growth phenotype and implicating Trm82p in maintaining levels of active Trm8p.
  RNA, 11, 821-830.  
16227259 J.Li, E.C.Fontaine-Rodriguez, and S.P.Whelan (2005).
Amino acid residues within conserved domain VI of the vesicular stomatitis virus large polymerase protein essential for mRNA cap methyltransferase activity.
  J Virol, 79, 13373-13384.  
15919887 V.Z.Grdzelishvili, S.Smallwood, D.Tower, R.L.Hall, D.M.Hunt, and S.A.Moyer (2005).
A single amino acid change in the L-polymerase protein of vesicular stomatitis virus completely abolishes viral mRNA cap methylation.
  J Virol, 79, 7327-7337.  
15375145 J.Hager, B.L.Staker, and U.Jakob (2004).
Substrate binding analysis of the 23S rRNA methyltransferase RrmJ.
  J Bacteriol, 186, 6634-6642.  
15238639 M.M.Slutsky, and E.N.Marsh (2004).
Cation-pi interactions studied in a model coiled-coil peptide.
  Protein Sci, 13, 2244-2251.  
12610118 X.Wu, and L.A.Guarino (2003).
Autographa californica nucleopolyhedrovirus orf69 encodes an RNA cap (nucleoside-2'-O)-methyltransferase.
  J Virol, 77, 3430-3440.  
12079779 A.Oguro, L.Johnson, and P.D.Gershon (2002).
Path of an RNA ligand around the surface of the vaccinia VP39 subunit of its cognate VP39-VP55 protein heterodimer.
  Chem Biol, 9, 679-690.  
12086624 C.M.Groft, and S.K.Burley (2002).
Recognition of eIF4G by rotavirus NSP3 reveals a basis for mRNA circularization.
  Mol Cell, 9, 1273-1283.
PDB code: 1lj2
12076527 F.Ferron, S.Longhi, B.Henrissat, and B.Canard (2002).
Viral RNA-polymerases -- a predicted 2'-O-ribose methyltransferase domain shared by all Mononegavirales.
  Trends Biochem Sci, 27, 222-224.  
12056895 G.D.Markham, P.O.Norrby, and C.W.Bock (2002).
S-adenosylmethionine conformations in solution and in protein complexes: conformational influences of the sulfonium group.
  Biochemistry, 41, 7636-7646.  
11918670 H.Hori, T.Suzuki, K.Sugawara, Y.Inoue, T.Shibata, S.Kuramitsu, S.Yokoyama, T.Oshima, and K.Watanabe (2002).
Identification and characterization of tRNA (Gm18) methyltransferase from Thermus thermophilus HB8: domain structure and conserved amino acid sequence motifs.
  Genes Cells, 7, 259-272.  
12181314 J.Hager, B.L.Staker, H.Bugl, and U.Jakob (2002).
Active site in RrmJ, a heat shock-induced methyltransferase.
  J Biol Chem, 277, 41978-41986.  
12032088 M.P.Egloff, D.Benarroch, B.Selisko, J.L.Romette, and B.Canard (2002).
An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization.
  EMBO J, 21, 2757-2768.
PDB codes: 1l9k 2p1d
12077432 O.Nureki, M.Shirouzu, K.Hashimoto, R.Ishitani, T.Terada, M.Tamakoshi, T.Oshima, M.Chijimatsu, K.Takio, D.G.Vassylyev, T.Shibata, Y.Inoue, S.Kuramitsu, and S.Yokoyama (2002).
An enzyme with a deep trefoil knot for the active-site architecture.
  Acta Crystallogr D Biol Crystallogr, 58, 1129-1137.
PDB code: 1ipa
11557810 X.Cheng, and R.J.Roberts (2001).
AdoMet-dependent methylation, DNA methyltransferases and base flipping.
  Nucleic Acids Res, 29, 3784-3795.  
10679461 F.A.Quiocho, G.Hu, and P.D.Gershon (2000).
Structural basis of mRNA cap recognition by proteins.
  Curr Opin Struct Biol, 10, 78-86.  
10983982 H.Bügl, E.B.Fauman, B.L.Staker, F.Zheng, S.R.Kushner, M.A.Saper, J.C.Bardwell, and U.Jakob (2000).
RNA methylation under heat shock control.
  Mol Cell, 6, 349-360.
PDB codes: 1eiz 1ej0
10654930 H.Wang, D.Boisvert, K.K.Kim, R.Kim, and S.H.Kim (2000).
Crystal structure of a fibrillarin homologue from Methanococcus jannaschii, a hyperthermophile, at 1.6 A resolution.
  EMBO J, 19, 317-323.
PDB code: 1fbn
9873020 A.Niewmierzycka, and S.Clarke (1999).
S-Adenosylmethionine-dependent methylation in Saccharomyces cerevisiae. Identification of a novel protein arginine methyltransferase.
  J Biol Chem, 274, 814-824.  
10029549 C.Schalk-Hihi, and G.D.Markham (1999).
The conformations of a substrate and a product bound to the active site of S-adenosylmethionine synthetase.
  Biochemistry, 38, 2542-2550.  
10377383 G.Hu, P.D.Gershon, A.E.Hodel, and F.A.Quiocho (1999).
mRNA cap recognition: dominant role of enhanced stacking interactions between methylated bases and protein aromatic side chains.
  Proc Natl Acad Sci U S A, 96, 7149-7154.
PDB codes: 1b42 1bky 1eam 1eqa 3mag 3mct 4dcg
9917067 J.Cavaillé, F.Chetouani, and J.P.Bachellerie (1999).
The yeast Saccharomyces cerevisiae YDL112w ORF encodes the putative 2'-O-ribose methyltransferase catalyzing the formation of Gm18 in tRNAs.
  RNA, 5, 66-81.  
10387078 Y.Hu, J.Komoto, Y.Huang, T.Gomi, H.Ogawa, Y.Takata, M.Fujioka, and F.Takusagawa (1999).
Crystal structure of S-adenosylhomocysteine hydrolase from rat liver.
  Biochemistry, 38, 8323-8333.
PDB code: 1b3r
9804844 A.M.Reeve, S.D.Breazeale, and C.A.Townsend (1998).
Purification, characterization, and cloning of an S-adenosylmethionine-dependent 3-amino-3-carboxypropyltransferase in nocardicin biosynthesis.
  J Biol Chem, 273, 30695-30703.  
  9628328 C.Schmutte, and P.A.Jones (1998).
Involvement of DNA methylation in human carcinogenesis.
  Biol Chem, 379, 377-388.  
9585521 D.E.Bussiere, S.W.Muchmore, C.G.Dealwis, G.Schluckebier, V.L.Nienaber, R.P.Edalji, K.A.Walter, U.S.Ladror, T.F.Holzman, and C.Abad-Zapatero (1998).
Crystal structure of ErmC', an rRNA methyltransferase which mediates antibiotic resistance in bacteria.
  Biochemistry, 37, 7103-7112.
PDB code: 2erc
  9696810 E.K.O'Reilly, Z.Wang, R.French, and C.C.Kao (1998).
Interactions between the structural domains of the RNA replication proteins of plant-infecting RNA viruses.
  J Virol, 72, 7160-7169.  
9582349 E.Rom, H.C.Kim, A.C.Gingras, J.Marcotrigiano, D.Favre, H.Olsen, S.K.Burley, and N.Sonenberg (1998).
Cloning and characterization of 4EHP, a novel mammalian eIF4E-related cap-binding protein.
  J Biol Chem, 273, 13104-13109.  
9665173 H.L.Schubert, K.S.Wilson, E.Raux, S.C.Woodcock, and M.J.Warren (1998).
The X-ray structure of a cobalamin biosynthetic enzyme, cobalt-precorrin-4 methyltransferase.
  Nat Struct Biol, 5, 585-592.
PDB codes: 1cbf 2cbf
9597750 H.Ogawa, T.Gomi, F.Takusagawa, and M.Fujioka (1998).
Structure, function and physiological role of glycine N-methyltransferase.
  Int J Biochem Cell Biol, 30, 13-26.  
  9811753 M.I.Vázquez, G.Rivas, D.Cregut, L.Serrano, and M.Esteban (1998).
The vaccinia virus 14-kilodalton (A27L) fusion protein forms a triple coiled-coil structure and interacts with the 21-kilodalton (A17L) virus membrane protein through a C-terminal alpha-helix.
  J Virol, 72, 10126-10137.  
9651316 M.Roth, S.Helm-Kruse, T.Friedrich, and A.Jeltsch (1998).
Functional roles of conserved amino acid residues in DNA methyltransferases investigated by site-directed mutagenesis of the EcoRV adenine-N6-methyltransferase.
  J Biol Chem, 273, 17333-17342.  
9501904 N.Sonenberg, S.K.Burley, and A.C.Gingras (1998).
RNA chiropractics.
  Nat Struct Biol, 5, 172-174.  
9862809 P.H.Tran, Z.R.Korszun, S.Cerritelli, S.S.Springhorn, and S.A.Lacks (1998).
Crystal structure of the DpnM DNA adenine methyltransferase from the DpnII restriction system of streptococcus pneumoniae bound to S-adenosylmethionine.
  Structure, 6, 1563-1575.
PDB code: 2dpm
9622508 S.W.Lockless, H.T.Cheng, A.E.Hodel, F.A.Quiocho, and P.D.Gershon (1998).
Recognition of capped RNA substrates by VP39, the vaccinia virus-encoded mRNA cap-specific 2'-O-methyltransferase.
  Biochemistry, 37, 8564-8574.  
9145102 A.E.Hodel, P.D.Gershon, X.Shi, S.M.Wang, and F.A.Quiocho (1997).
Specific protein recognition of an mRNA cap through its alkylated base.
  Nat Struct Biol, 4, 350-354.
PDB codes: 1p39 1v39 1vp3 1vp9 2vp3
9188741 A.V.Efimov (1997).
Structural trees for protein superfamilies.
  Proteins, 28, 241-260.  
9261078 G.Varani (1997).
A cap for all occasions.
  Structure, 5, 855-858.  
9187657 L.Yu, A.M.Petros, A.Schnuchel, P.Zhong, J.M.Severin, K.Walter, T.F.Holzman, and S.W.Fesik (1997).
Solution structure of an rRNA methyltransferase (ErmAM) that confers macrolide-lincosamide-streptogramin antibiotic resistance.
  Nat Struct Biol, 4, 483-489.
PDB code: 1yub
9115443 S.Djordjevic, and A.M.Stock (1997).
Crystal structure of the chemotaxis receptor methyltransferase CheR suggests a conserved structural motif for binding S-adenosylmethionine.
  Structure, 5, 545-558.
PDB code: 1af7
  8985362 T.Ahola, P.Laakkonen, H.Vihinen, and L.Kääriäinen (1997).
Critical residues of Semliki Forest virus RNA capping enzyme involved in methyltransferase and guanylyltransferase-like activities.
  J Virol, 71, 392-397.  
9287339 X.Shi, T.G.Bernhardt, S.M.Wang, and P.D.Gershon (1997).
The surface region of the bifunctional vaccinia RNA modifying protein VP39 that interfaces with Poly(A) polymerase is remote from the RNA binding cleft used for its mRNA 5' cap methylation function.
  J Biol Chem, 272, 23292-23302.  
8807872 H.C.Nelson, and T.H.Bestor (1996).
Base eversion and shuffling by DNA methyltransferases.
  Chem Biol, 3, 419-423.  
8939751 M.M.Dixon, S.Huang, R.G.Matthews, and M.Ludwig (1996).
The structure of the C-terminal domain of methionine synthase: presenting S-adenosylmethionine for reductive methylation of B12.
  Structure, 4, 1263-1275.
PDB code: 1msk
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 codes are shown on the right.