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Hydrolase PDB id
2bhr
Jmol
Contents
Protein chains
431 a.a. *
Ligands
SO4 ×2
Waters ×141
* Residue conservation analysis
PDB id:
2bhr
Name: Hydrolase
Title: Dengue virus RNA helicase
Structure: RNA helicase. Chain: a, b. Fragment: residues 1646-2093. Engineered: yes
Source: Dengue virus 2. Organism_taxid: 11060. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_variant: codon plus. Other_details: ay037116, nucleotides 5032-6301
Resolution:
2.80Å     R-factor:   0.204     R-free:   0.252
Authors: T.Xu,A.Sampath,A.Chao,D.Wen,M.Nanao,P.Chene,S.G.Vasudevan, J
Key ref: T.Xu et al. (2005). Structure of the Dengue virus helicase/nucleoside triphosphatase catalytic domain at a resolution of 2.4 A. J Virol, 79, 10278-10288. PubMed id: 16051821 DOI: 10.1128/JVI.79.16.10278-10288.2005
Date:
17-Jan-05     Release date:   03-Aug-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q91H74  (Q91H74_9FLAV) -  Polyprotein
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		3391 a.a.
431 a.a.
Key:    PfamA domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     viral genome replication   1 term 
  Biochemical function     nucleic acid binding     4 terms  

 

 
DOI no: 10.1128/JVI.79.16.10278-10288.2005 J Virol 79:10278-10288 (2005)
PubMed id: 16051821  
 
 
Structure of the Dengue virus helicase/nucleoside triphosphatase catalytic domain at a resolution of 2.4 A.
T.Xu, A.Sampath, A.Chao, D.Wen, M.Nanao, P.Chene, S.G.Vasudevan, J.Lescar.
 
  ABSTRACT  
 
Dengue fever is an important emerging public health concern, with several million viral infections occurring annually, for which no effective therapy currently exists. The NS3 protein from Dengue virus is a multifunctional protein of 69 kDa, endowed with protease, helicase, and nucleoside 5'-triphosphatase (NTPase) activities. Thus, NS3 plays an important role in viral replication and represents a very interesting target for the development of specific antiviral inhibitors. We present the structure of an enzymatically active fragment of the Dengue virus NTPase/helicase catalytic domain to 2.4 A resolution. The structure is composed of three domains, displays an asymmetric distribution of charges on its surface, and contains a tunnel large enough to accommodate single-stranded RNA. Its C-terminal domain adopts a new fold compared to the NS3 helicase of hepatitis C virus, which has interesting implications for the evolution of the Flaviviridae replication complex. A bound sulfate ion reveals residues involved in the metal-dependent NTPase catalytic mechanism. Comparison with the NS3 hepatitis C virus helicase complexed to single-stranded DNA would place the 3' single-stranded tail of a nucleic acid duplex in the tunnel that runs across the basic face of the protein. A possible model for the unwinding mechanism is proposed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21358811 J.M.Doolittle, and S.M.Gomez (2011).
Mapping Protein Interactions between Dengue Virus and Its Human and Insect Hosts.
  PLoS Negl Trop Dis, 5, e954.  
20978807 S.A.Shiryaev, A.V.Chernov, T.N.Shiryaeva, A.E.Aleshin, and A.Y.Strongin (2011).
The acidic sequence of the NS4A cofactor regulates ATP hydrolysis by the HCV NS3 helicase.
  Arch Virol, 156, 313-318.  
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.  
  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.  
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.  
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.  
18796313 A.Sampath, and R.Padmanabhan (2009).
Molecular targets for flavivirus drug discovery.
  Antiviral Res, 81, 6.  
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
  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.  
19694536 M.S.Diamond (2009).
Mechanisms of evasion of the type I interferon antiviral response by flaviviruses.
  J Interferon Cytokine Res, 29, 521-530.  
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
18698358 A.M.Khan, O.Miotto, E.J.Nascimento, K.N.Srinivasan, A.T.Heiny, G.L.Zhang, E.T.Marques, T.W.Tan, V.Brusic, J.Salmon, and J.T.August (2008).
Conservation and variability of dengue virus proteins: implications for vaccine design.
  PLoS Negl Trop Dis, 2, e272.  
18199634 C.G.Patkar, and R.J.Kuhn (2008).
Yellow Fever virus NS3 plays an essential role in virus assembly independent of its known enzymatic functions.
  J Virol, 82, 3342-3352.  
17942558 D.Luo, T.Xu, C.Hunke, G.Grüber, S.G.Vasudevan, and J.Lescar (2008).
Crystal structure of the NS3 protease-helicase from dengue virus.
  J Virol, 82, 173-183.
PDB code: 2vbc
19008861 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, and J.Lescar (2008).
Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 protein.
  EMBO J, 27, 3209-3219.
PDB codes: 2jlq 2jlr 2jls 2jlu 2jlv 2jlw 2jlx 2jly 2jlz
18042258 K.Werme, M.Wigerius, and M.Johansson (2008).
Tick-borne encephalitis virus NS5 associates with membrane protein scribble and impairs interferon-stimulated JAK-STAT signalling.
  Cell Microbiol, 10, 696-712.  
18644250 R.Perera, and R.J.Kuhn (2008).
Structural proteomics of dengue virus.
  Curr Opin Microbiol, 11, 369-377.  
18235970 R.Qi, L.Zhang, and C.W.Chi (2008).
Biological characteristics of dengue virus and potential targets for drug design.
  Acta Biochim Biophys Sin (Shanghai), 40, 91.  
18004778 S.Speroni, L.De Colibus, E.Mastrangelo, E.Gould, B.Coutard, N.L.Forrester, S.Blanc, B.Canard, and A.Mattevi (2008).
Structure and biochemical analysis of Kokobera virus helicase.
  Proteins, 70, 1120-1123.
PDB codes: 2v6i 2v6j
17893366 E.J.Mancini, R.Assenberg, A.Verma, T.S.Walter, R.Tuma, J.M.Grimes, R.J.Owens, and D.I.Stuart (2007).
Structure of the Murray Valley encephalitis virus RNA helicase at 1.9 Angstrom resolution.
  Protein Sci, 16, 2294-2300.
PDB code: 2v8o
17574830 E.Jankowsky, and M.E.Fairman (2007).
RNA helicases--one fold for many functions.
  Curr Opin Struct Biol, 17, 316-324.  
17705192 J.Bordignon, D.M.Strottmann, A.L.Mosimann, C.M.Probst, V.Stella, L.Noronha, S.M.Zanata, and C.N.Dos Santos (2007).
Dengue neurovirulence in mice: identification of molecular signatures in the E and NS3 helicase domains.
  J Med Virol, 79, 1506-1517.  
17301157 S.A.Shiryaev, B.I.Ratnikov, A.E.Aleshin, I.A.Kozlov, N.A.Nelson, M.Lebl, J.W.Smith, R.C.Liddington, and A.Y.Strongin (2007).
Switching the substrate specificity of the two-component NS2B-NS3 flavivirus proteinase by structure-based mutagenesis.
  J Virol, 81, 4501-4509.  
17301146 T.L.Yap, T.Xu, Y.L.Chen, H.Malet, M.P.Egloff, B.Canard, S.G.Vasudevan, and J.Lescar (2007).
Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-angstrom resolution.
  J Virol, 81, 4753-4765.
PDB codes: 2j7u 2j7w
17400272 V.L.Reichert, M.Choi, J.E.Petrillo, and L.Gehrke (2007).
Alfalfa mosaic virus coat protein bridges RNA and RNA-dependent RNA polymerase in vitro.
  Virology, 364, 214-226.  
16775356 A.Sampath, T.Xu, A.Chao, D.Luo, J.Lescar, and S.G.Vasudevan (2006).
Structure-based mutational analysis of the NS3 helicase from dengue virus.
  J Virol, 80, 6686-6690.  
  16946468 E.Mastrangelo, M.Bollati, M.Milani, N.Brisbarre, X.de Lamballerie, B.Coutard, B.Canard, A.Khromykh, and M.Bolognesi (2006).
Preliminary crystallographic characterization of an RNA helicase from Kunjin virus.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 876-879.  
17085042 J.R.Mesters, J.Tan, and R.Hilgenfeld (2006).
Viral enzymes.
  Curr Opin Struct Biol, 16, 776-786.  
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.