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PDBsum entry 2w2g

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protein ligands Protein-protein interface(s) links
RNA-binding protein PDB id
2w2g
Jmol
Contents
Protein chains
257 a.a. *
Ligands
SO4 ×2
Waters ×178
* Residue conservation analysis
PDB id:
2w2g
Name: RNA-binding protein
Title: Human sars coronavirus unique domain
Structure: Non-structural protein 3. Chain: a, b. Fragment: sars unique domain, residues 1207-1470. Synonym: papain-like proteinase, replicase polyprotein 1a, orf1a polyprotein. Engineered: yes. Mutation: yes
Source: Sars coronavirus. Organism_taxid: 227859. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.22Å     R-factor:   0.214     R-free:   0.268
Authors: J.Tan,C.Vonrhein,O.S.Smart,G.Bricogne,M.Bollati,Y.Kusov, G.Hansen,J.R.Mesters,C.L.Schmidt,R.Hilgenfeld
Key ref: J.Tan et al. (2009). The SARS-unique domain (SUD) of SARS coronavirus contains two macrodomains that bind G-quadruplexes. PLoS Pathog, 5, e1000428. PubMed id: 19436709
Date:
30-Oct-08     Release date:   26-May-09    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0C6U8  (R1A_CVHSA) -  Replicase polyprotein 1a
Seq:
Struc:
 
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Seq:
Struc:
4382 a.a.
257 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: 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 2: E.C.3.4.22.69  - Sars coronavirus main proteinase.
[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.

 

 
PLoS Pathog 5:e1000428 (2009)
PubMed id: 19436709  
 
 
The SARS-unique domain (SUD) of SARS coronavirus contains two macrodomains that bind G-quadruplexes.
J.Tan, C.Vonrhein, O.S.Smart, G.Bricogne, M.Bollati, Y.Kusov, G.Hansen, J.R.Mesters, C.L.Schmidt, R.Hilgenfeld.
 
  ABSTRACT  
 
Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARS-unique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389-652 ("SUD(core)") of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 A resolution, respectively) revealed that SUD(core) forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD(core) as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5-6 nucleotides, but more extended G-stretches are found in the 3'-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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
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
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.