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PDBsum entry 1l1n

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protein Protein-protein interface(s) links
Viral protein, hydrolase PDB id
1l1n
Jmol
Contents
Protein chains
180 a.a. *
Waters ×135
* Residue conservation analysis
PDB id:
1l1n
Name: Viral protein, hydrolase
Title: Poliovirus 3c proteinase
Structure: Genome polyprotein: picornain 3c. Chain: a, b. Fragment: residues 1565-1747. Synonym: protease 3c, p3c. Engineered: yes
Source: Human poliovirus 1. Organism_taxid: 12081. Strain: mahoney. Gene: 3c. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
2.10Å     R-factor:   0.213     R-free:   0.259
Authors: S.C.Mosimann,M.M.Chernaia,S.Sia,S.Plotch,M.N.G.James
Key ref:
S.C.Mosimann et al. (1997). Refined X-ray crystallographic structure of the poliovirus 3C gene product. J Mol Biol, 273, 1032-1047. PubMed id: 9367789 DOI: 10.1006/jmbi.1997.1306
Date:
19-Feb-02     Release date:   10-Apr-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P03300  (POLG_POL1M) -  Genome polyprotein
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2209 a.a.
180 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.2.7.7.48  - RNA-directed Rna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
Nucleoside triphosphate
+ RNA(n)
= diphosphate
+ RNA(n+1)
   Enzyme class 3: E.C.3.4.22.28  - Picornain 3C.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
   Enzyme class 4: E.C.3.4.22.29  - Picornain 2A.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Selective cleavage of Tyr-|-Gly bond in the picornavirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
   Enzyme class 5: E.C.3.6.1.15  - Nucleoside-triphosphate phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: NTP + H2O = NDP + phosphate
NTP
+ H(2)O
= NDP
+ phosphate
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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     catalytic activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.1997.1306 J Mol Biol 273:1032-1047 (1997)
PubMed id: 9367789  
 
 
Refined X-ray crystallographic structure of the poliovirus 3C gene product.
S.C.Mosimann, M.M.Cherney, S.Sia, S.Plotch, M.N.James.
 
  ABSTRACT  
 
The X-ray crystallographic structure of the recombinant poliovirus 3C gene product (Mahoney strain) has been determined by single isomorphous replacement and non-crystallographic symmetry averaging and refined at 2.1 A resolution. Poliovirus 3C is comprised of two six-stranded antiparallel beta-barrel domains and is structurally similar to the chymotrypsin-like serine proteinases. The shallow active site cleft is located at the junction of the two beta-barrel domains and contains a His40, Glu71, Cys147 catalytic triad. The polypeptide loop preceding Cys147 is flexible and likely undergoes a conformational change upon substrate binding. The specificity pockets for poliovirus 3C are well-defined and modeling studies account for the known substrate specificity of this proteinase. Poliovirus 3C also participates in the formation of the viral replicative initiation complex where it specifically recognizes and binds the RNA stem-loop structure in the 5' non-translated region of its own genome. The RNA recognition site of 3C is located on the opposite side of the molecule in relation to its proteolytic active site and is centered about the conserved KFRDIR sequence of the domain linker. The recognition site is well-defined and also includes residues from the amino and carboxy-terminal helices. The two molecules in the asymmetric unit are related by an approximate 2-fold, non-crystallographic symmetry and form an intermolecular antiparallel beta-sheet at their interface.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. A stereo depiction of the active site cleft of PV-3C molecule A. His40 of helix B, Glu71 of β-strand fI and Cys147 preceding β-strand dII comprise a catalytic triad similar to the His-Asp-Ser triad of chymotrypsin-like serine proteinases. Gly145 N and Cys147 N form the oxyanion hole and residues 140 to 146 form one side of the active site cleft. Residues Val162, Gly163, Gly164 and Asn165 of β-strand e2II line the base of the cleft and His161 lies at the bottom of the S[1] pocket. β-strands bI and bII contribute residues to the S′[n] and S[n] sites of the active site cleft, respectively.
Figure 8.
Figure 8. The immediate environment of Tyr138 in molecule A (thick lines) and B (thin lines) is represented as a stereo diagram. The Tyr138 side-chain is completely buried in the hydrophobic core and adopts slightly different conformations in the two molecules. In either conformation, the hydrogen atom of the Tyr138 OH can lie in the plane of the His161 imidazole and is able to form a strong hydrogen bond with the acceptor lone-pair electrons of N^δ1.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 273, 1032-1047) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21396941 S.Cui, J.Wang, T.Fan, B.Qin, L.Guo, X.Lei, J.Wang, M.Wang, and Q.Jin (2011).
Crystal structure of human enterovirus 71 3C protease.
  J Mol Biol, 408, 449-461.
PDB code: 3osy
20521933 C.E.Cameron, H.Suk Oh, and I.M.Moustafa (2010).
Expanding knowledge of P3 proteins in the poliovirus lifecycle.
  Future Microbiol, 5, 867-881.  
20066739 X.N.Zhang, Z.G.Song, T.Jiang, B.S.Shi, Y.W.Hu, and Z.H.Yuan (2010).
Rupintrivir is a promising candidate for treating severe cases of Enterovirus-71 infection.
  World J Gastroenterol, 16, 201-209.  
19779565 K.F.Weng, M.L.Li, C.T.Hung, and S.R.Shih (2009).
Enterovirus 71 3C protease cleaves a novel target CstF-64 and inhibits cellular polyadenylation.
  PLoS Pathog, 5, e1000593.  
18305026 C.D.Amero, J.J.Arnold, I.M.Moustafa, C.E.Cameron, and M.P.Foster (2008).
Identification of the oriI-binding site of poliovirus 3C protein by nuclear magnetic resonance spectroscopy.
  J Virol, 82, 4363-4370.  
18420805 L.M.Hales, N.J.Knowles, P.S.Reddy, L.Xu, C.Hay, and P.L.Hallenbeck (2008).
Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus.
  J Gen Virol, 89, 1265-1275.  
17993457 M.Shen, Z.J.Reitman, Y.Zhao, I.Moustafa, Q.Wang, J.J.Arnold, H.B.Pathak, and C.E.Cameron (2008).
Picornavirus genome replication. Identification of the surface of the poliovirus (PV) 3C dimer that interacts with PV 3Dpol during VPg uridylylation and construction of a structural model for the PV 3C2-3Dpol complex.
  J Biol Chem, 283, 875-888.  
17567696 G.A.Belov, C.Habbersett, D.Franco, and E.Ehrenfeld (2007).
Activation of cellular Arf GTPases by poliovirus protein 3CD correlates with virus replication.
  J Virol, 81, 9259-9267.  
17392285 H.B.Pathak, J.J.Arnold, P.N.Wiegand, M.R.Hargittai, and C.E.Cameron (2007).
Picornavirus genome replication: assembly and organization of the VPg uridylylation ribonucleoprotein (initiation) complex.
  J Biol Chem, 282, 16202-16213.  
17459920 K.S.Colletti, K.E.Smallenburg, Y.Xu, and G.S.Pari (2007).
Human cytomegalovirus UL84 interacts with an RNA stem-loop sequence found within the RNA/DNA hybrid region of oriLyt.
  J Virol, 81, 7077-7085.  
17251299 L.L.Marcotte, A.B.Wass, D.W.Gohara, H.B.Pathak, J.J.Arnold, D.J.Filman, C.E.Cameron, and J.M.Hogle (2007).
Crystal structure of poliovirus 3CD protein: virally encoded protease and precursor to the RNA-dependent RNA polymerase.
  J Virol, 81, 3583-3596.
PDB codes: 2ijd 2ijf
17537861 P.Florez de Sessions, E.Dobrikova, and M.Gromeier (2007).
Genetic adaptation to untranslated region-mediated enterovirus growth deficits by mutations in the nonstructural proteins 3AB and 3CD.
  J Virol, 81, 8396-8405.  
16979372 S.Curry, N.Roqué-Rosell, P.A.Zunszain, and R.J.Leatherbarrow (2007).
Foot-and-mouth disease virus 3C protease: recent structural and functional insights into an antiviral target.
  Int J Biochem Cell Biol, 39, 1-6.  
17459935 T.Oka, M.Yamamoto, M.Yokoyama, S.Ogawa, G.S.Hansman, K.Katayama, K.Miyashita, H.Takagi, Y.Tohya, H.Sato, and N.Takeda (2007).
Highly conserved configuration of catalytic amino acid residues among calicivirus-encoded proteases.
  J Virol, 81, 6798-6806.  
17065215 T.R.Sweeney, N.Roqué-Rosell, J.R.Birtley, R.J.Leatherbarrow, and S.Curry (2007).
Structural and mutagenic analysis of foot-and-mouth disease virus 3C protease reveals the role of the beta-ribbon in proteolysis.
  J Virol, 81, 115-124.
PDB code: 2j92
17266160 Z.Suo, and M.A.Abdullah (2007).
Unique Composite Active Site of the Hepatitis C Virus NS2-3 Protease: a New Opportunity for Antiviral Drug Design.
  ChemMedChem, 2, 283-284.  
16973591 A.Nayak, I.G.Goodfellow, K.E.Woolaway, J.Birtley, S.Curry, and G.J.Belsham (2006).
Role of RNA structure and RNA binding activity of foot-and-mouth disease virus 3C protein in VPg uridylylation and virus replication.
  J Virol, 80, 9865-9875.  
16641296 C.E.Zeitler, M.K.Estes, and B.V.Venkataram Prasad (2006).
X-ray crystallographic structure of the Norwalk virus protease at 1.5-A resolution.
  J Virol, 80, 5050-5058.
PDB codes: 2fyq 2fyr
16862121 I.C.Lorenz, J.Marcotrigiano, T.G.Dentzer, and C.M.Rice (2006).
Structure of the catalytic domain of the hepatitis C virus NS2-3 protease.
  Nature, 442, 831-835.
PDB code: 2hd0
17085042 J.R.Mesters, J.Tan, and R.Hilgenfeld (2006).
Viral enzymes.
  Curr Opin Struct Biol, 16, 776-786.  
16895471 M.N.James (2006).
The peptidases from fungi and viruses.
  Biol Chem, 387, 1023-1029.  
16571831 S.L.Smits, E.J.Snijder, and R.J.de Groot (2006).
Characterization of a torovirus main proteinase.
  J Virol, 80, 4157-4167.  
16894217 W.J.Melchers, J.Zoll, M.Tessari, D.V.Bakhmutov, A.P.Gmyl, V.I.Agol, and H.A.Heus (2006).
A GCUA tetranucleotide loop found in the poliovirus oriL by in vivo SELEX (un)expectedly forms a YNMG-like structure: Extending the YNMG family with GYYA.
  RNA, 12, 1671-1682.
PDB code: 2evy
  16300678 D.Franco, H.B.Pathak, C.E.Cameron, B.Rombaut, E.Wimmer, and A.V.Paul (2005).
Stimulation of poliovirus RNA synthesis and virus maturation in a HeLa cell-free in vitro translation-RNA replication system by viral protein 3CDpro.
  Virol J, 2, 86.  
15858279 J.R.Birtley, and S.Curry (2005).
Crystallization of foot-and-mouth disease virus 3C protease: surface mutagenesis and a novel crystal-optimization strategy.
  Acta Crystallogr D Biol Crystallogr, 61, 646-650.  
15654079 J.R.Birtley, S.R.Knox, A.M.Jaulent, P.Brick, R.J.Leatherbarrow, and S.Curry (2005).
Crystal structure of foot-and-mouth disease virus 3C protease. New insights into catalytic mechanism and cleavage specificity.
  J Biol Chem, 280, 11520-11527.
PDB code: 2bhg
16227288 K.Nakamura, Y.Someya, T.Kumasaka, G.Ueno, M.Yamamoto, T.Sato, N.Takeda, T.Miyamura, and N.Tanaka (2005).
A norovirus protease structure provides insights into active and substrate binding site integrity.
  J Virol, 79, 13685-13693.
PDB code: 1wqs
15306852 A.A.Thompson, and O.B.Peersen (2004).
Structural basis for proteolysis-dependent activation of the poliovirus RNA-dependent RNA polymerase.
  EMBO J, 23, 3462-3471.
PDB codes: 1ra6 1ra7 1raj 1tql
15254188 M.Kuyumcu-Martinez, G.Belliot, S.V.Sosnovtsev, K.O.Chang, K.Y.Green, and R.E.Lloyd (2004).
Calicivirus 3C-like proteinase inhibits cellular translation by cleavage of poly(A)-binding protein.
  J Virol, 78, 8172-8182.  
15308719 R.Banerjee, M.K.Weidman, A.Echeverri, P.Kundu, and A.Dasgupta (2004).
Regulation of poliovirus 3C protease by the 2C polypeptide.
  J Virol, 78, 9243-9256.  
14966374 S.R.Shih, C.Chiang, T.C.Chen, C.N.Wu, J.T.Hsu, J.C.Lee, M.J.Hwang, M.L.Li, G.W.Chen, and M.S.Ho (2004).
Mutations at KFRDI and VGK domains of enterovirus 71 3C protease affect its RNA binding and proteolytic activities.
  J Biomed Sci, 11, 239-248.  
14711816 Y.Yang, R.Rijnbrand, S.Watowich, and S.M.Lemon (2004).
Genetic evidence for an interaction between a picornaviral cis-acting RNA replication element and 3CD protein.
  J Biol Chem, 279, 12659-12667.  
12502857 J.Ziebuhr, S.Bayer, J.A.Cowley, and A.E.Gorbalenya (2003).
The 3C-like proteinase of an invertebrate nidovirus links coronavirus and potyvirus homologs.
  J Virol, 77, 1415-1426.  
12824164 K.M.Connolly, B.T.Smith, R.Pilpa, U.Ilangovan, M.E.Jung, and R.T.Clubb (2003).
Sortase from Staphylococcus aureus does not contain a thiolate-imidazolium ion pair in its active site.
  J Biol Chem, 278, 34061-34065.  
12525179 Z.Sárkány, and L.Polgár (2003).
The unusual catalytic triad of poliovirus protease 3C.
  Biochemistry, 42, 516-522.  
12377789 J.Phan, A.Zdanov, A.G.Evdokimov, J.E.Tropea, H.K.Peters, R.B.Kapust, M.Li, A.Wlodawer, and D.S.Waugh (2002).
Structural basis for the substrate specificity of tobacco etch virus protease.
  J Biol Chem, 277, 50564-50572.
PDB codes: 1lvb 1lvm
12093723 K.Anand, G.J.Palm, J.R.Mesters, S.G.Siddell, J.Ziebuhr, and R.Hilgenfeld (2002).
Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain.
  EMBO J, 21, 3213-3224.
PDB code: 1lvo
12021327 Y.Someya, N.Takeda, and T.Miyamura (2002).
Identification of active-site amino acid residues in the Chiba virus 3C-like protease.
  J Virol, 76, 5949-5958.  
11260254 K.Hara, M.Shiota, H.Kido, Y.Ohtsu, T.Kashiwagi, J.Iwahashi, N.Hamada, K.Mizoue, N.Tsumura, H.Kato, and T.Toyoda (2001).
Influenza virus RNA polymerase PA subunit is a novel serine protease with Ser624 at the active site.
  Genes Cells, 6, 87-97.  
11044080 A.V.Paul, E.Rieder, D.W.Kim, J.H.van Boom, and E.Wimmer (2000).
Identification of an RNA hairpin in poliovirus RNA that serves as the primary template in the in vitro uridylylation of VPg.
  J Virol, 74, 10359-10370.  
10500110 A.R.Khan, N.Khazanovich-Bernstein, E.M.Bergmann, and M.N.James (1999).
Structural aspects of activation pathways of aspartic protease zymogens and viral 3C protease precursors.
  Proc Natl Acad Sci U S A, 96, 10968-10975.  
10500114 D.A.Matthews, P.S.Dragovich, S.E.Webber, S.A.Fuhrman, A.K.Patick, L.S.Zalman, T.F.Hendrickson, R.A.Love, T.J.Prins, J.T.Marakovits, R.Zhou, J.Tikhe, C.E.Ford, J.W.Meador, R.A.Ferre, E.L.Brown, S.L.Binford, M.A.Brothers, D.M.DeLisle, and S.T.Worland (1999).
Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes.
  Proc Natl Acad Sci U S A, 96, 11000-11007.
PDB code: 1cqq
10523291 J.F.Petersen, M.M.Cherney, H.D.Liebig, T.Skern, E.Kuechler, and M.N.James (1999).
The structure of the 2A proteinase from a common cold virus: a proteinase responsible for the shut-off of host-cell protein synthesis.
  EMBO J, 18, 5463-5475.
PDB code: 2hrv
10212275 T.B.Parsley, C.T.Cornell, and B.L.Semler (1999).
Modulation of the RNA binding and protein processing activities of poliovirus polypeptide 3CD by the viral RNA polymerase domain.
  J Biol Chem, 274, 12867-12876.  
10092679 T.G.Lawson, D.L.Gronros, P.E.Evans, M.C.Bastien, K.M.Michalewich, J.K.Clark, J.H.Edmonds, K.H.Graber, J.A.Werner, B.A.Lurvey, and J.M.Cate (1999).
Identification and characterization of a protein destruction signal in the encephalomyocarditis virus 3C protease.
  J Biol Chem, 274, 9871-9880.  
  9658124 P.Gallinari, D.Brennan, C.Nardi, M.Brunetti, L.Tomei, C.Steinkühler, and R.De Francesco (1998).
Multiple enzymatic activities associated with recombinant NS3 protein of hepatitis C virus.
  J Virol, 72, 6758-6769.  
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.