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PDBsum entry 1av6

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protein dna_rna ligands links
Transferase/RNA PDB id
1av6
Jmol
Contents
Protein chain
289 a.a. *
DNA/RNA
Ligands
MGT
SAH
* Residue conservation analysis
PDB id:
1av6
Name: Transferase/RNA
Title: Vaccinia methyltransferase vp39 complexed with m7g capped rn and s-adenosylhomocysteine
Structure: RNA (5'-r( Gp Ap Ap Ap Ap A)-3'). Chain: b. Synonym: 5' capped RNA hexamer. Engineered: yes. Cap-specific mRNA (nucleoside-2'-o-)-methyltransf chain: a. Synonym: poly(a) polymerase regulatory subunit, poly(a) pol small subunit, pap-s, vp39. Engineered: yes.
Source: Vaccinia virus wr. Vacv. Organism_taxid: 10254. Strain: western reserve. Gene: paps, vacwr095, f9. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Monomer (from PDB file)
Resolution:
2.80Å     R-factor:   0.215     R-free:   0.285
Authors: A.E.Hodel,P.D.Gershon,F.A.Quiocho
Key ref:
A.E.Hodel et al. (1998). Structural basis for sequence-nonspecific recognition of 5'-capped mRNA by a cap-modifying enzyme. Mol Cell, 1, 443-447. PubMed id: 9660928 DOI: 10.1016/S1097-2765(00)80044-1
Date:
26-Sep-97     Release date:   25-Feb-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P07617  (MCE_VACCW) -  Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase
Seq:
Struc:
333 a.a.
289 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.1.1.57  - 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)
S-adenosyl-L-methionine
+ 5'-(N(7)-methyl 5'-triphosphoguanosine)- (purine-ribonucleotide)-(mRNA)
Bound ligand (Het Group name = MGT)
matches with 47.00% similarity
=
S-adenosyl-L-homocysteine
Bound ligand (Het Group name = SAH)
corresponds exactly
+ 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!
  Biological process     mRNA capping   2 terms 
  Biochemical function     translation elongation factor activity     2 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/S1097-2765(00)80044-1 Mol Cell 1:443-447 (1998)
PubMed id: 9660928  
 
 
Structural basis for sequence-nonspecific recognition of 5'-capped mRNA by a cap-modifying enzyme.
A.E.Hodel, P.D.Gershon, F.A.Quiocho.
 
  ABSTRACT  
 
Sequence-nonspecific binding of RNA, recognition of a 7-methylguanosine 5' mRNA cap, and methylation of a nucleic acid backbone are three crucial and ubiquitous events in eukaryotic nucleic acid processing and function. These three events occur concurrently in the modification of vaccinia transcripts by the methyltransferase VP39. We report the crystal structure of a ternary complex comprising VP39, coenzyme product S-adenosylhomocysteine, and a 5' m7 G-capped, single-stranded RNA hexamer. This structure reveals a novel and general mechanism for sequence-non-specific recognition of the mRNA transcript in which the protein interacts solely with the sugar-phosphate backbone of a short, single-stranded RNA helix. This report represents the first direct and detailed view of a protein complexed with single-stranded RNA or 5'-capped mRNA.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Electron Density for the First Trimer of RNA Bound in the Methyltransferase Active SiteThe 2.7 Å density is calculated as a 2F[o] − F[c] map using only the protein model to calculate the phases. Contoured at 1σ, only the density near the RNA is displayed for clarity. The surrounding atoms of the protein are shown without density for context. This figure was rendered using RIBBONS ([5]).
Figure 2.
Figure 2. mRNA–VP39 Complex(A) Stick model showing RNA bound to the active site cleft of VP39. The protein is rendered as a solvent-accessible surface. The sulfur atom of AdoHcy (colored green and labeled with an arrow) defines the methyltransferase active site.(B) The two RNA contacts mapped on a single VP39 molecule resulting from the interaction of the RNA with two symmetry-related protein molecules. The protein is rendered as a transparent solvent-accessible surface. Shown in front of the protein is the second trimer (A4-A5-A6) binding site based on the interactions with a symmetry-related molecule. Behind the protein are the 5′ cap and the first trimer (G1-A2-A3) of the transcript bound in the methyltransferase active site.(C) The proximity of the second RNA contact site to the VP55 dimerization interface. The major red patch denotes surface residues defined in [20] as the VP55 dimerization 'hot spot.' The smaller red patch (R107 to the right) is another part of the dimerization interface (see [20]). This figure was produced using GRASP ( [17]).
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (1998, 1, 443-447) copyright 1998.  

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.  
20383144 K.Das, J.M.Aramini, L.C.Ma, R.M.Krug, and E.Arnold (2010).
Structures of influenza A proteins and insights into antiviral drug targets.
  Nat Struct Mol Biol, 17, 530-538.  
20639534 M.F.Soulière, J.P.Perreault, and M.Bisaillon (2010).
Insights into the molecular determinants involved in cap recognition by the vaccinia virus D10 decapping enzyme.
  Nucleic Acids Res, 38, 7599-7610.  
20007328 R.Jain, and S.Shuman (2010).
Bacterial Hen1 is a 3' terminal RNA ribose 2'-O-methyltransferase component of a bacterial RNA repair cassette.
  RNA, 16, 316-323.  
19052078 A.M.Murphy, and V.Z.Grdzelishvili (2009).
Identification of sendai virus L protein amino acid residues affecting viral mRNA cap methylation.
  J Virol, 83, 1669-1681.  
19504740 J.R.Zamudio, B.Mittra, D.A.Campbell, and N.R.Sturm (2009).
Hypermethylated cap 4 maximizes Trypanosoma brucei translation.
  Mol Microbiol, 72, 1100-1110.  
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.  
19217398 M.Wu, P.Nilsson, N.Henriksson, A.Niedzwiecka, M.K.Lim, Z.Cheng, K.Kokkoris, A.Virtanen, and H.Song (2009).
Structural basis of m(7)GpppG binding to poly(A)-specific ribonuclease.
  Structure, 17, 276-286.
PDB code: 3d45
19750007 S.S.Bradrick, and M.Gromeier (2009).
Identification of gemin5 as a novel 7-methylguanosine cap-binding protein.
  PLoS One, 4, e7030.  
19386620 T.Monecke, A.Dickmanns, and R.Ficner (2009).
Structural basis for m7G-cap hypermethylation of small nuclear, small nucleolar and telomerase RNA by the dimethyltransferase TGS1.
  Nucleic Acids Res, 37, 3865-3877.
PDB code: 3gdh
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.  
18454157 D.Guilligay, F.Tarendeau, P.Resa-Infante, R.Coloma, T.Crepin, P.Sehr, J.Lewis, R.W.Ruigrok, J.Ortin, D.J.Hart, and S.Cusack (2008).
The structural basis for cap binding by influenza virus polymerase subunit PB2.
  Nat Struct Mol Biol, 15, 500-506.
PDB code: 2vqz
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.  
18928538 I.Y.Tcherepanova, M.D.Adams, X.Feng, A.Hinohara, J.Horvatinovich, D.Calderhead, D.Healey, and C.A.Nicolette (2008).
Ectopic expression of a truncated CD40L protein from synthetic post-transcriptionally capped RNA in dendritic cells induces high levels of IL-12 secretion.
  BMC Mol Biol, 9, 90.  
18280238 M.V.Deshmukh, B.N.Jones, D.U.Quang-Dang, J.Flinders, S.N.Floor, C.Kim, J.Jemielity, M.Kalek, E.Darzynkiewicz, and J.D.Gross (2008).
mRNA decapping is promoted by an RNA-binding channel in Dcp2.
  Mol Cell, 29, 324-336.
PDB code: 2jvb
18632949 P.Roy (2008).
Bluetongue virus: dissection of the polymerase complex.
  J Gen Virol, 89, 1789-1804.  
17473012 E.Mastrangelo, M.Bollati, M.Milani, B.Selisko, F.Peyrane, B.Canard, G.Grard, X.de 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
17301144 H.Dong, D.Ray, S.Ren, B.Zhang, F.Puig-Basagoiti, Y.Takagi, C.K.Ho, H.Li, and P.Y.Shi (2007).
Distinct RNA elements confer specificity to flavivirus RNA cap methylation events.
  J Virol, 81, 4412-4421.  
17785461 P.Nilsson, N.Henriksson, A.Niedzwiecka, N.A.Balatsos, K.Kokkoris, J.Eriksson, and A.Virtanen (2007).
A multifunctional RNA recognition motif in poly(A)-specific ribonuclease with cap and poly(A) binding properties.
  J Biol Chem, 282, 32902-32911.  
17416901 Y.Takagi, S.Sindkar, D.Ekonomidis, M.P.Hall, and C.K.Ho (2007).
Trypanosoma brucei encodes a bifunctional capping enzyme essential for cap 4 formation on the spliced leader RNA.
  J Biol Chem, 282, 15995-16005.  
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
16886072 A.Schmidt, A.Lindner, M.Nieger, M.d.e.l. .C.Ruiz-Delgado, and F.J.Ramirez (2006).
Syntheses, pi-stacking interactions and base-pairings of uracil pyridinium salts and uracilyl betaines with nucleobases.
  Org Biomol Chem, 4, 3056-3066.  
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.  
16433904 K.L.Tkaczuk, A.Obarska, and J.M.Bujnicki (2006).
Molecular phylogenetics and comparative modeling of HEN1, a methyltransferase involved in plant microRNA biogenesis.
  BMC Evol Biol, 6, 6.  
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.  
15375145 J.Hager, B.L.Staker, and U.Jakob (2004).
Substrate binding analysis of the 23S rRNA methyltransferase RrmJ.
  J Bacteriol, 186, 6634-6642.  
15362228 N.Cougot, E.van Dijk, S.Babajko, and B.Séraphin (2004).
'Cap-tabolism'.
  Trends Biochem Sci, 29, 436-444.  
14573618 G.Hu, A.L.Tsai, and F.A.Quiocho (2003).
Insertion of an N7-methylguanine mRNA cap between two coplanar aromatic residues of a cap-binding protein is fast and selective for a positively charged cap.
  J Biol Chem, 278, 51515-51520.  
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.  
12454499 C.Mazza, A.Segref, I.W.Mattaj, and S.Cusack (2002).
Co-crystallization of the human nuclear cap-binding complex with a m7GpppG cap analogue using protein engineering.
  Acta Crystallogr D Biol Crystallogr, 58, 2194-2197.  
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.  
12377117 G.Michel, V.Sauvé, R.Larocque, Y.Li, A.Matte, and M.Cygler (2002).
The structure of the RlmB 23S rRNA methyltransferase reveals a new methyltransferase fold with a unique knot.
  Structure, 10, 1303-1315.
PDB code: 1gz0
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.  
11927565 L.Pintard, F.Lecointe, J.M.Bujnicki, C.Bonnerot, H.Grosjean, and B.Lapeyre (2002).
Trm7p catalyses the formation of two 2'-O-methylriboses in yeast tRNA anticodon loop.
  EMBO J, 21, 1811-1820.  
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
11937063 S.Bailey, S.E.Sedelnikova, G.M.Blackburn, H.M.Abdelghany, P.J.Baker, A.G.McLennan, and J.B.Rafferty (2002).
The crystal structure of diadenosine tetraphosphate hydrolase from Caenorhabditis elegans in free and binary complex forms.
  Structure, 10, 589-600.
PDB codes: 1kt9 1ktg
11545740 C.Mazza, M.Ohno, A.Segref, I.W.Mattaj, and S.Cusack (2001).
Crystal structure of the human nuclear cap binding complex.
  Mol Cell, 8, 383-396.
PDB code: 1h6k
  11574057 J.M.Bujnicki, and L.Rychlewski (2001).
Reassignment of specificities of two cap methyltransferase domains in the reovirus lambda 2 protein.
  Genome Biol, 2, RESEARCH0038.  
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.  
10676814 H.A.Lewis, K.Musunuru, K.B.Jensen, C.Edo, H.Chen, R.B.Darnell, and S.K.Burley (2000).
Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome.
  Cell, 100, 323-332.
PDB code: 1ec6
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
11080641 M.M.Skinner, J.M.Puvathingal, R.L.Walter, and A.M.Friedman (2000).
Crystal structure of protein isoaspartyl methyltransferase: a catalyst for protein repair.
  Structure, 8, 1189-1201.
PDB code: 1dl5
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
9860948 S.Niranjanakumari, T.Stams, S.M.Crary, D.W.Christianson, and C.A.Fierke (1998).
Protein component of the ribozyme ribonuclease P alters substrate recognition by directly contacting precursor tRNA.
  Proc Natl Acad Sci U S A, 95, 15212-15217.  
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.