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PDBsum entry 2jlx
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protein dna_rna ligands metals Protein-protein interface(s) links
Hydrolase/RNA PDB id
2jlx

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
451 a.a. *
DNA/RNA
Ligands
ADP-VO4 ×2
Metals
_MN ×2
_CL
Waters ×384
* Residue conservation analysis
PDB id:
2jlx
Name: Hydrolase/RNA
Title: Dengue virus 4 ns3 helicase in complex with ssrna and adp-vanadate
Structure: Serine protease subunit ns3. Chain: a, b. Fragment: residues 1646-2092. Synonym: denv4 ns3 helicase, non-structural protein 3. Engineered: yes. 5'-r( Ap Gp Ap Cp Up Ap Ap Cp Ap Ap Cp U)-3'. Chain: c, d. Engineered: yes
Source: Dengue virus 4. Organism_taxid: 408688. Strain: thailand/0348/1991. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes
Resolution:
2.20Å     R-factor:   0.198     R-free:   0.245
Authors: D.H.Luo,T.Xu,R.P.Watson,D.S.Becker,A.Sampath,W.Jahnke,S.S.Yeong, C.H.Wang,S.P.Lim,S.G.Vasudevan,J.Lescar
Key ref: D.Luo et al. (2008). Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 protein. Embo J, 27, 3209-3219. PubMed id: 19008861
Date:
15-Sep-08     Release date:   25-Nov-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q2YHF0  (POLG_DEN4T) -  Genome polyprotein from Dengue virus type 4 (strain Thailand/0348/1991)
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		3387 a.a.
451 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 10 residue positions (black crosses)

DNA/RNA chains
  A-G-A-C-U-A-A-C 8 bases
  A-G-A-C-U-A-A-C 8 bases

 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
 = 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA
 +
S-adenosyl-L-homocysteine
Bound ligand (Het Group name = ADP)
matches with 51.43% similarity
   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
 = 5'-end (N(7)-methyl 5'-triphosphoguanosine)- (2'-O-methyl-ribonucleoside) in mRNA
 + S-adenosyl-L-homocysteine
 + H(+)
Bound ligand (Het Group name = ADP)
matches with 51.43% similarity
   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
 + H2O
 =
ADP
Bound ligand (Het Group name = ADP)
corresponds exactly 		+ 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    
 
 
Embo J 27:3209-3219 (2008)
PubMed id: 19008861  
 
 
Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 protein.
D.Luo, T.Xu, R.P.Watson, D.Scherer-Becker, A.Sampath, W.Jahnke, S.S.Yeong, C.H.Wang, S.P.Lim, A.Strongin, S.G.Vasudevan, J.Lescar.
 
  ABSTRACT  
 
Together with the NS5 polymerase, the NS3 helicase has a pivotal function in flavivirus RNA replication and constitutes an important drug target. We captured the dengue virus NS3 helicase at several stages along the catalytic pathway including bound to single-stranded (ss) RNA, to an ATP analogue, to a transition-state analogue and to ATP hydrolysis products. RNA recognition appears largely sequence independent in a way remarkably similar to eukaryotic DEAD box proteins Vasa and eIF4AIII. On ssRNA binding, the NS3 enzyme switches to a catalytic-competent state imparted by an inward movement of the P-loop, interdomain closure and a change in the divalent metal coordination shell, providing a structural basis for RNA-stimulated ATP hydrolysis. These structures demonstrate for the first time large quaternary changes in the flaviviridae helicase, identify the catalytic water molecule and point to a beta-hairpin that protrudes from subdomain 2, as a critical element for dsRNA unwinding. They also suggest how NS3 could exert an effect as an RNA-anchoring device and thus participate both in flavivirus RNA replication and assembly.
 

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.  
20108979 C.A.Belon, Y.D.High, T.I.Lin, F.Pauwels, and D.N.Frick (2010).
Mechanism and specificity of a symmetrical benzimidazolephenylcarboxamide helicase inhibitor.
  Biochemistry, 49, 1822-1832.  
20512115 H.Walbott, S.Mouffok, R.Capeyrou, S.Lebaron, O.Humbert, H.van Tilbeurgh, Y.Henry, and N.Leulliot (2010).
Prp43p contains a processive helicase structural architecture with a specific regulatory domain.
  EMBO J, 29, 2194-2204.
PDB code: 2xau
  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
20080715 M.Gu, and C.M.Rice (2010).
Three conformational snapshots of the hepatitis C virus NS3 helicase reveal a ratchet translocation mechanism.
  Proc Natl Acad Sci U S A, 107, 521-528.
PDB codes: 3kqh 3kqk 3kql 3kqn 3kqu
21085466 N.J.Moreland, M.Y.Tay, E.Lim, P.N.Paradkar, D.N.Doan, Y.H.Yau, S.Geifman Shochat, and S.G.Vasudevan (2010).
High affinity human antibody fragments to dengue virus non-structural protein 3.
  PLoS Negl Trop Dis, 4, e881.  
  21076642 S.A.Shiryaev, and A.Y.Strongin (2010).
Structural and functional parameters of the flaviviral protease: a promising antiviral drug target.
  Future Virol, 5, 593-606.  
20421212 S.Despins, M.Issur, I.Bougie, and M.Bisaillon (2010).
Deciphering the molecular basis for nucleotide selection by the West Nile virus RNA helicase.
  Nucleic Acids Res, 38, 5493-5506.  
20192763 W.Yang (2010).
Lessons learned from UvrD helicase: mechanism for directional movement.
  Annu Rev Biophys, 39, 367-385.  
20168331 Y.He, G.R.Andersen, and K.H.Nielsen (2010).
Structural basis for the function of DEAH helicases.
  EMBO Rep, 11, 180-186.
PDB code: 3kx2
  20165556 B.J.Geiss, H.Stahla, A.M.Hannah, H.H.Gari, and S.M.Keenan (2009).
Focus on flaviviruses: current and future drug targets.
  Future Med Chem, 1, 327.  
19332076 C.A.Belon, and D.N.Frick (2009).
Fuel specificity of the hepatitis C virus NS3 helicase.
  J Mol Biol, 388, 851-864.  
  20161209 C.A.Belon, and D.N.Frick (2009).
Helicase inhibitors as specifically targeted antiviral therapy for hepatitis C.
  Future Virol, 4, 277-293.  
  19555498 D.Vlachakis (2009).
Theoretical study of the Usutu virus helicase 3D structure, by means of computer-aided homology modelling.
  Theor Biol Med Model, 6, 9.  
19748356 M.Del Campo, and A.M.Lambowitz (2009).
Structure of the Yeast DEAD box protein Mss116p reveals two wedges that crimp RNA.
  Mol Cell, 35, 598-609.
PDB codes: 3i5x 3i5y 3i61 3i62
19692542 R.A.Agis-Juárez, I.Galván, F.Medina, T.Daikoku, R.Padmanabhan, J.E.Ludert, and R.M.del Angel (2009).
Polypyrimidine tract-binding protein is relocated to the cytoplasm and is required during dengue virus infection in Vero cells.
  J Gen Virol, 90, 2893-2901.  
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
19474250 S.A.Shiryaev, A.V.Chernov, A.E.Aleshin, T.N.Shiryaeva, and A.Y.Strongin (2009).
NS4A regulates the ATPase activity of the NS3 helicase: a novel cofactor role of the non-structural protein NS4A from West Nile virus.
  J Gen Virol, 90, 2081-2085.  
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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