PDBsum entry 1jsz

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Transferase PDB id
Protein chain
291 a.a. *
Waters ×166
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure analysis of n7,9-dimethylguanine-vp39 complex
Structure: Vp39. Chain: a. Fragment: residues 1-307. Synonym: poly(a) polymerase regulatory subunit. Engineered: yes
Source: Vaccinia virus. Organism_taxid: 10245. Expressed in: escherichia coli. Expression_system_taxid: 562
1.93Å     R-factor:   0.210     R-free:   0.252
Authors: G.Hu,A.Oguro,P.D.Gershon,F.A.Quiocho
Key ref:
G.Hu et al. (2002). The "cap-binding slot" of an mRNA cap-binding protein: quantitative effects of aromatic side chain choice in the double-stacking sandwich with cap. Biochemistry, 41, 7677-7687. PubMed id: 12056899 DOI: 10.1021/bi0201926
19-Aug-01     Release date:   10-Jul-02    
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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

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     virion   1 term 
  Biological process     methylation   8 terms 
  Biochemical function     transferase activity     5 terms  


DOI no: 10.1021/bi0201926 Biochemistry 41:7677-7687 (2002)
PubMed id: 12056899  
The "cap-binding slot" of an mRNA cap-binding protein: quantitative effects of aromatic side chain choice in the double-stacking sandwich with cap.
G.Hu, A.Oguro, C.Li, P.D.Gershon, F.A.Quiocho.
The N7-methylguanine portion of the mRNA cap structure interacts with cap-binding proteins via an unusual double-stacking arrangement in which the positively charged cap is sandwiched between two parallel-oriented aromatic protein side chains. Three-dimensional costructures of cap with two mRNA cap-binding proteins, namely, translational initiation factor eIF4E and VP39 (the vaccinia virus-encoded mRNA cap-specific 2'-O-methyltransferase), have heretofore been reported. Despite striking similarities between the two proteins in the double stack with the cap, the stack differs most notably in the species of stacked side chain donated by the protein. Whereas eIF4E employs two tryptophans, VP39 uses a tyrosine and a phenylalanine. Here, we have generated tryptophan substitutions in VP39. Tryptophan substitution was shown, crystallographically, not to disrupt the maintenance of a bona fide parallel stack. However, the single-tryptophan and double-tryptophan substitutions were associated with increased affinity for cap nucleoside by factors of 10 and 50, respectively. VP39 interacted more strongly with a true substrate (containing portions of RNA downstream of the cap in addition to the cap itself) than with isolated cap nucleoside, by several orders of magnitude. VP39 mutants with tryptophan substitution at position 180 exhibited apparent defects in substrate catalytic rate during the first turnover cycle, indicating the possibility of an exquisite sensitivity of the catalytic center to subtle changes in substrate position brought about by alterations in the cap-binding slot. The X-ray structure of VP39 with a genuine nucleobase analogue of N7-methylguanosine, namely, N7,9-dimethylguanine, indicated that the N7-methylguanosine rotational orientation within the stack is a property of the cap nucleobase itself.

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.  
19926722 D.Benarroch, M.Jankowska-Anyszka, J.Stepinski, E.Darzynkiewicz, and S.Shuman (2010).
Cap analog substrates reveal three clades of cap guanine-N2 methyltransferases with distinct methyl acceptor specificities.
  RNA, 16, 211-220.  
20360394 J.Chang, B.Schwer, and S.Shuman (2010).
Mutational analyses of trimethylguanosine synthase (Tgs1) and Mud2: proteins implicated in pre-mRNA splicing.
  RNA, 16, 1018-1031.  
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.  
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.  
18186485 R.Worch, and R.Stolarski (2008).
Stacking efficiency and flexibility analysis of aromatic amino acids in cap-binding proteins.
  Proteins, 71, 2026-2037.  
15920472 A.Strasser, A.Dickmanns, R.Lührmann, and R.Ficner (2005).
Structural basis for m3G-cap-mediated nuclear import of spliceosomal UsnRNPs by snurportin1.
  EMBO J, 24, 2235-2243.
PDB code: 1xk5
15597333 J.Tang, H.Naitow, N.A.Gardner, A.Kolesar, L.Tang, R.B.Wickner, and J.E.Johnson (2005).
The structural basis of recognition and removal of cellular mRNA 7-methyl G 'caps' by a viral capsid protein: a unique viral response to host defense.
  J Mol Recognit, 18, 158-168.  
15277671 G.Zolotnitsky, U.Cogan, N.Adir, V.Solomon, G.Shoham, and Y.Shoham (2004).
Mapping glycoside hydrolase substrate subsites by isothermal titration calorimetry.
  Proc Natl Acad Sci U S A, 101, 11275-11280.
PDB codes: 1r85 1r87
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.  
12646557 P.Fechter, L.Mingay, J.Sharps, A.Chambers, E.Fodor, and G.G.Brownlee (2003).
Two aromatic residues in the PB2 subunit of influenza A RNA polymerase are crucial for cap binding.
  J Biol Chem, 278, 20381-20388.  
14732928 R.L.Rich, and D.G.Myszka (2003).
A survey of the year 2002 commercial optical biosensor literature.
  J Mol Recognit, 16, 351-382.  
12445771 D.D.Boehr, A.R.Farley, G.D.Wright, and J.R.Cox (2002).
Analysis of the pi-pi stacking interactions between the aminoglycoside antibiotic kinase APH(3')-IIIa and its nucleotide ligands.
  Chem Biol, 9, 1209-1217.  
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.  
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.