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PDBsum entry 2fav
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Viral protein PDB id
2fav

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
172 a.a. *
Ligands
APR
Waters ×432
* Residue conservation analysis
PDB id:
2fav
Name: Viral protein
Title: Crystal structure of sars macro domain in complex with adp-ribose at 1.8 a resolution
Structure: Replicase polyprotein 1ab (pp1ab) (orf1ab). Chain: a, b, c. Fragment: 1000-1173 of pp1a. Engineered: yes
Source: Sars coronavirus. Organism_taxid: 227859. Strain: frankfurt 1. Gene: nsp3. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.80Å     R-factor:   0.164     R-free:   0.206
Authors: M.P.Egloff,H.Malet,Marseilles Structural Genomics Program @ Afmb (Msgp)
Key ref: M.P.Egloff et al. (2006). Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains. J Virol, 80, 8493-8502. PubMed id: 16912299
Date:
08-Dec-05     Release date:   10-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0C6X7  (R1AB_CVHSA) -  Replicase polyprotein 1ab from Severe acute respiratory syndrome coronavirus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
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Seq:
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Seq:
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Seq:
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Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		7073 a.a.
172 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.2.1.1.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 3: 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
   Enzyme class 4: 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(+)
   Enzyme class 5: 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)
Bound ligand (Het Group name = APR)
matches with 75.00% similarity 		+ diphosphate
   Enzyme class 6: E.C.2.7.7.50  - mRNA guanylyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a 5'-end diphospho-ribonucleoside in mRNA + GTP + H+ = a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + diphosphate
5'-end diphospho-ribonucleoside in mRNA
 + GTP
 + H(+)
 = 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA
 + diphosphate
   Enzyme class 7: E.C.3.1.13.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 8: E.C.3.4.19.12  - ubiquitinyl hydrolase 1.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Thiol-dependent hydrolysis of ester, thiolester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
   Enzyme class 9: E.C.3.4.22.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 10: E.C.3.4.22.69  - Sars coronavirus main proteinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 11: E.C.3.6.4.12  - Dna helicase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate + H+
ATP
 + H2O
 = ADP
 + phosphate
 + H(+)
   Enzyme class 12: E.C.3.6.4.13  - Rna helicase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate + H+
ATP
 + H2O
 = ADP
 + phosphate
 + H(+)
   Enzyme class 13: E.C.4.6.1.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
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    
 
 
J Virol 80:8493-8502 (2006)
PubMed id: 16912299  
 
 
Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains.
M.P.Egloff, H.Malet, A.Putics, M.Heinonen, H.Dutartre, A.Frangeul, A.Gruez, V.Campanacci, C.Cambillau, J.Ziebuhr, T.Ahola, B.Canard.
 
  ABSTRACT  
 
Macro domains constitute a protein module family found associated with specific histones and proteins involved in chromatin metabolism. In addition, a small number of animal RNA viruses, such as corona- and toroviruses, alphaviruses, and hepatitis E virus, encode macro domains for which, however, structural and functional information is extremely limited. Here, we characterized the macro domains from hepatitis E virus, Semliki Forest virus, and severe acute respiratory syndrome coronavirus (SARS-CoV). The crystal structure of the SARS-CoV macro domain was determined at 1.8-Angstroms resolution in complex with ADP-ribose. Information derived from structural, mutational, and sequence analyses suggests a close phylogenetic and, most probably, functional relationship between viral and cellular macro domain homologs. The data revealed that viral macro domains have relatively poor ADP-ribose 1"-phosphohydrolase activities (which were previously proposed to be their biologically relevant function) but bind efficiently free and poly(ADP-ribose) polymerase 1-bound poly(ADP-ribose) in vitro. Collectively, these results suggest to further evaluate the role of viral macro domains in host response to viral infection.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20976195 B.F.Beitzel, R.R.Bakken, J.M.Smith, and C.S.Schmaljohn (2010).
High-resolution functional mapping of the venezuelan equine encephalitis virus genome by insertional mutagenesis and massively parallel sequencing.
  PLoS Pathog, 6, e1001146.  
20668085 H.L.Stokes, S.Baliji, C.G.Hui, S.G.Sawicki, S.C.Baker, and S.G.Siddell (2010).
A new cistron in the murine hepatitis virus replicase gene.
  J Virol, 84, 10148-10158.  
20660183 K.R.Hurst, R.Ye, S.J.Goebel, P.Jayaraman, and P.S.Masters (2010).
An interaction between the nucleocapsid protein and a component of the replicase-transcriptase complex is crucial for the infectivity of coronavirus genomic RNA.
  J Virol, 84, 10276-10288.  
20015978 M.Varjak, E.Zusinaite, and A.Merits (2010).
Novel functions of the alphavirus nonstructural protein nsP3 C-terminal region.
  J Virol, 84, 2352-2364.  
20369302 S.J.Bender, and S.R.Weiss (2010).
Pathogenesis of murine coronavirus in the central nervous system.
  J Neuroimmune Pharmacol, 5, 336-354.  
20071563 Y.A.Karpe, and K.S.Lole (2010).
NTPase and 5' to 3' RNA duplex-unwinding activities of the hepatitis E virus helicase domain.
  J Virol, 84, 3595-3602.  
19052085 A.Chatterjee, M.A.Johnson, P.Serrano, B.Pedrini, J.S.Joseph, B.W.Neuman, K.Saikatendu, M.J.Buchmeier, P.Kuhn, and K.Wüthrich (2009).
Nuclear magnetic resonance structure shows that the severe acute respiratory syndrome coronavirus-unique domain contains a macrodomain fold.
  J Virol, 83, 1823-1836.
PDB codes: 2jzd 2jze 2jzf 2rnk
19515826 E.Park, and D.E.Griffin (2009).
Interaction of Sindbis virus non-structural protein 3 with poly(ADP-ribose) polymerase 1 in neuronal cells.
  J Gen Virol, 90, 2073-2080.  
19395054 E.Park, and D.E.Griffin (2009).
The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice.
  Virology, 388, 305-314.  
19625413 H.A.Basta, S.B.Cleveland, R.A.Clinton, A.G.Dimitrov, and M.A.McClure (2009).
Evolution of teleost fish retroviruses: characterization of new retroviruses with cellular genes.
  J Virol, 83, 10152-10162.  
19386706 H.Malet, B.Coutard, S.Jamal, H.Dutartre, N.Papageorgiou, M.Neuvonen, T.Ahola, N.Forrester, E.A.Gould, D.Lafitte, F.Ferron, J.Lescar, A.E.Gorbalenya, X.de Lamballerie, and B.Canard (2009).
The crystal structures of Chikungunya and Venezuelan equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket.
  J Virol, 83, 6534-6545.
PDB codes: 3gpg 3gpo 3gpq 3gqe 3gqo
19966415 J.A.Wojdyla, I.Manolaridis, E.J.Snijder, A.E.Gorbalenya, B.Coutard, Y.Piotrowski, R.Hilgenfeld, and P.A.Tucker (2009).
Structure of the X (ADRP) domain of nsp3 from feline coronavirus.
  Acta Crystallogr D Biol Crystallogr, 65, 1292-1300.
PDB codes: 3eti 3ew5 3jzt
19436709 J.Tan, C.Vonrhein, O.S.Smart, G.Bricogne, M.Bollati, Y.Kusov, G.Hansen, J.R.Mesters, C.L.Schmidt, and R.Hilgenfeld (2009).
The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes.
  PLoS Pathog, 5, e1000428.
PDB codes: 2w2g 2wct
20221421 K.M.Rose, and S.R.Weiss (2009).
Murine Coronavirus Cell Type Dependent Interaction with the Type I Interferon Response.
  Viruses, 1, 689-712.  
19828617 P.Serrano, M.A.Johnson, A.Chatterjee, B.W.Neuman, J.S.Joseph, M.J.Buchmeier, P.Kuhn, and K.Wüthrich (2009).
Nuclear magnetic resonance structure of the nucleic acid-binding domain of severe acute respiratory syndrome coronavirus nonstructural protein 3.
  J Virol, 83, 12998-13008.
PDB code: 2k87
19177346 Y.Piotrowski, G.Hansen, A.L.Boomaars-van der Zanden, E.J.Snijder, A.E.Gorbalenya, and R.Hilgenfeld (2009).
Crystal structures of the X-domains of a Group-1 and a Group-3 coronavirus reveal that ADP-ribose-binding may not be a conserved property.
  Protein Sci, 18, 6.
PDB codes: 3ejf 3ejg 3eke
18987156 Y.Xu, L.Cong, C.Chen, L.Wei, Q.Zhao, X.Xu, Y.Ma, M.Bartlam, and Z.Rao (2009).
Crystal structures of two coronavirus ADP-ribose-1''-monophosphatases and their complexes with ADP-Ribose: a systematic structural analysis of the viral ADRP domain.
  J Virol, 83, 1083-1092.
PDB codes: 3ewo 3ewp 3ewq 3ewr
18069692 A.Hakmé, A.Huber, P.Dollé, and V.Schreiber (2008).
The macroPARP genes parp-9 and parp-14 are developmentally and differentially regulated in mouse tissues.
  Dev Dyn, 237, 209-215.  
18927583 A.Hakmé, H.K.Wong, F.Dantzer, and V.Schreiber (2008).
The expanding field of poly(ADP-ribosyl)ation reactions. 'Protein Modifications: Beyond the Usual Suspects' Review Series.
  EMBO Rep, 9, 1094-1100.  
18981049 J.P.Gagné, M.Isabelle, K.S.Lo, S.Bourassa, M.J.Hendzel, V.L.Dawson, T.M.Dawson, and G.G.Poirier (2008).
Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes.
  Nucleic Acids Res, 36, 6959-6976.  
18922871 K.K.Eriksson, L.Cervantes-Barragán, B.Ludewig, and V.Thiel (2008).
Mouse hepatitis virus liver pathology is dependent on ADP-ribose-1''-phosphatase, a viral function conserved in the alpha-like supergroup.
  J Virol, 82, 12325-12334.  
18156685 M.Bartlam, X.Xue, and Z.Rao (2008).
The search for a structural basis for therapeutic intervention against the SARS coronavirus.
  Acta Crystallogr A, 64, 204-213.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
18596091 V.Lulla, D.L.Sawicki, S.G.Sawicki, A.Lulla, A.Merits, and T.Ahola (2008).
Molecular defects caused by temperature-sensitive mutations in Semliki Forest virus nsP1.
  J Virol, 82, 9236-9244.  
17251282 J.Ziebuhr, B.Schelle, N.Karl, E.Minskaia, S.Bayer, S.G.Siddell, A.E.Gorbalenya, and V.Thiel (2007).
Human coronavirus 229E papain-like proteases have overlapping specificities but distinct functions in viral replication.
  J Virol, 81, 3922-3932.  
17680348 M.Bartlam, Y.Xu, and Z.Rao (2007).
Structural proteomics of the SARS coronavirus: a model response to emerging infectious diseases.
  J Struct Funct Genomics, 8, 85-97.  
  17931416 S.Mattiussi, I.Tempera, G.Matusali, G.Mearini, L.Lenti, S.Fratarcangeli, L.Mosca, M.D'Erme, and E.Mattia (2007).
Inhibition of Poly(ADP-ribose)polymerase impairs Epstein Barr Virus lytic cycle progression.
  Infect Agent Cancer, 2, 18.  
16987966 H.Schütze, R.Ulferts, B.Schelle, S.Bayer, H.Granzow, B.Hoffmann, T.C.Mettenleiter, and J.Ziebuhr (2006).
Characterization of White bream virus reveals a novel genetic cluster of nidoviruses.
  J Virol, 80, 11598-11609.  
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.

 

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