PDBsum entry 1qol

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Hydrolase PDB id
Protein chains
(+ 2 more) 166 a.a. *
EDO ×3
_CL ×3
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Structure of the fmdv leader protease
Structure: Protease (nonstructural protein p20a). Chain: a, b, c, d, e, f, g, h. Synonym: leader protease. Engineered: yes. Mutation: yes
Source: Foot-and-mouth disease virus. Organism_taxid: 73482. Strain: o1. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
3.0Å     R-factor:   0.258     R-free:   0.314
Authors: A.Guarne,J.Tormo,R.Kirchweger,D.Pfistermueller,T.Skern, I.Fita
Key ref: A.Guarné et al. (1998). Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and eIF4G recognition. EMBO J, 17, 7469-7479. PubMed id: 9857201
13-Nov-99     Release date:   10-Nov-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P03305  (POLG_FMDVO) -  Genome polyprotein
2332 a.a.
166 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: E.C.  - 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 2: E.C.  - 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 3: E.C.  - L-peptidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Autocatalytically cleaves itself from the polyprotein of the foot-and-mouth disease virus by hydrolysis of a Lys-|-Gly bond, but then cleaves host cell initiation factor eIF-4G at bonds -Gly-|-Arg- and -Lys-|-Arg-.
   Enzyme class 4: E.C.  - Nucleoside-triphosphate phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: NTP + H2O = NDP + phosphate
+ H(2)O
+ 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     viral reproduction   2 terms 
  Biochemical function     cysteine-type endopeptidase activity     1 term  


EMBO J 17:7469-7479 (1998)
PubMed id: 9857201  
Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and eIF4G recognition.
A.Guarné, J.Tormo, R.Kirchweger, D.Pfistermueller, I.Fita, T.Skern.
The leader protease of foot-and-mouth disease virus, as well as cleaving itself from the nascent viral polyprotein, disables host cell protein synthesis by specific proteolysis of a cellular protein: the eukaryotic initiation factor 4G (eIF4G). The crystal structure of the leader protease presented here comprises a globular catalytic domain reminiscent of that of cysteine proteases of the papain superfamily, and a flexible C-terminal extension found intruding into the substrate-binding site of an adjacent molecule. Nevertheless, the relative disposition of this extension and the globular domain to each other supports intramolecular self-processing. The different sequences of the two substrates cleaved during viral replication, the viral polyprotein (at LysLeuLys/GlyAlaGly) and eIF4G (at AsnLeuGly/ArgThrThr), appear to be recognized by distinct features in a narrow, negatively charged groove traversing the active centre. The structure illustrates how the prototype papain fold has been adapted to the requirements of an RNA virus. Thus, the protein scaffold has been reduced to a minimum core domain, with the active site being modified to increase specificity. Furthermore, surface features have been developed which enable C-terminal self-processing from the viral polyprotein.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21541224 A.Castelló, E.Alvarez, and L.Carrasco (2011).
The Multifaceted Poliovirus 2A Protease: Regulation of Gene Expression by Picornavirus Proteases.
  J Biomed Biotechnol, 2011, 369648.  
20410261 F.Xue, Y.Sun, L.Yan, C.Zhao, J.Chen, M.Bartlam, X.Li, Z.Lou, and Z.Rao (2010).
The crystal structure of porcine reproductive and respiratory syndrome virus nonstructural protein Nsp1beta reveals a novel metal-dependent nuclease.
  J Virol, 84, 6461-6471.
PDB code: 3mtv
20519455 Miranda, B.Dainat, B.Locke, G.Cordoni, H.Berthoud, L.Gauthier, P.Neumann, G.E.Budge, B.V.Ball, and D.B.Stoltz (2010).
Genetic characterization of slow bee paralysis virus of the honeybee (Apis mellifera L.).
  J Gen Virol, 91, 2524-2530.  
19863558 S.V.Hato, F.Sorgeloos, C.Ricour, J.Zoll, W.J.Melchers, T.Michiels, and F.J.van Kuppeveld (2010).
Differential IFN-alpha/beta production suppressing capacities of the leader proteins of mengovirus and foot-and-mouth disease virus.
  Cell Microbiol, 12, 310-317.  
19430121 S.B.Nagendrakumar, M.Madhanmohan, P.N.Rangarajan, and V.A.Srinivasan (2009).
Genetic analysis of foot-and-mouth disease virus serotype A of Indian origin and detection of positive selection and recombination in leader protease-and capsid-coding regions.
  J Biosci, 34, 85.  
19052079 los Santos, F.D.Segundo, J.Zhu, M.Koster, C.C.Dias, and M.J.Grubman (2009).
A conserved domain in the leader proteinase of foot-and-mouth disease virus is required for proper subcellular localization and function.
  J Virol, 83, 1800-1810.  
19706710 Y.Sun, F.Xue, Y.Guo, M.Ma, N.Hao, X.C.Zhang, Z.Lou, X.Li, and Z.Rao (2009).
Crystal structure of porcine reproductive and respiratory syndrome virus leader protease Nsp1alpha.
  J Virol, 83, 10931-10940.
PDB code: 3ifu
18305051 C.Mayer, D.Neubauer, A.T.Nchinda, R.Cencic, K.Trompf, and T.Skern (2008).
Residue L143 of the foot-and-mouth disease virus leader proteinase is a determinant of cleavage specificity.
  J Virol, 82, 4656-4659.  
17728223 A.Vagnozzi, D.A.Stein, P.L.Iversen, and E.Rieder (2007).
Inhibition of foot-and-mouth disease virus infections in cell cultures with antisense morpholino oligomers.
  J Virol, 81, 11669-11680.  
17475644 Y.Zhou, W.P.Tzeng, W.Yang, Y.Zhou, Y.Ye, H.W.Lee, T.K.Frey, and J.Yang (2007).
Identification of a Ca2+-binding domain in the rubella virus nonstructural protease.
  J Virol, 81, 7517-7528.  
16641291 G.Lanzi, Miranda, M.B.Boniotti, C.E.Cameron, A.Lavazza, L.Capucci, S.M.Camazine, and C.Rossi (2006).
Molecular and biological characterization of deformed wing virus of honeybees (Apis mellifera L.).
  J Virol, 80, 4998-5009.  
16377622 S.Ishii, T.Yano, and H.Hayashi (2006).
Expression and characterization of the peptidase domain of Streptococcus pneumoniae ComA, a bifunctional ATP-binding cassette transporter involved in quorum sensing pathway.
  J Biol Chem, 281, 4726-4731.  
16358325 T.Sulea, H.A.Lindner, E.O.Purisima, and R.Ménard (2006).
Binding site-based classification of coronaviral papain-like proteases.
  Proteins, 62, 760-775.  
16077010 K.K.Kojima, and H.Fujiwara (2005).
An extraordinary retrotransposon family encoding dual endonucleases.
  Genome Res, 15, 1106-1117.  
15885108 N.Foeger, E.Kuehnel, R.Cencic, and T.Skern (2005).
The binding of foot-and-mouth disease virus leader proteinase to eIF4GI involves conserved ionic interactions.
  FEBS J, 272, 2602-2611.  
15016848 A.Gradi, N.Foeger, R.Strong, Y.V.Svitkin, N.Sonenberg, T.Skern, and G.J.Belsham (2004).
Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro.
  J Virol, 78, 3271-3278.  
15084510 M.J.Grubman, and B.Baxt (2004).
Foot-and-mouth disease.
  Clin Microbiol Rev, 17, 465-493.  
15388929 X.Carpena, W.Melik-Adamyan, P.C.Loewen, and I.Fita (2004).
Structure of the C-terminal domain of the catalase-peroxidase KatG from Escherichia coli.
  Acta Crystallogr D Biol Crystallogr, 60, 1824-1832.
PDB codes: 1u2j 1u2k 1u2l
12791690 N.Foeger, E.M.Schmid, and T.Skern (2003).
Human rhinovirus 2 2Apro recognition of eukaryotic initiation factor 4GI. Involvement of an exosite.
  J Biol Chem, 278, 33200-33207.  
12663811 W.Glaser, A.Triendl, and T.Skern (2003).
The processing of eIF4GI by human rhinovirus type 2 2A(pro): relationship to self-cleavage and role of zinc.
  J Virol, 77, 5021-5025.  
12486817 C.F.Basler, and A.García-Sastre (2002).
Viruses and the type I interferon antiviral system: induction and evasion.
  Int Rev Immunol, 21, 305-337.  
12228254 N.Foeger, W.Glaser, and T.Skern (2002).
Recognition of eukaryotic initiation factor 4G isoforms by picornaviral proteinases.
  J Biol Chem, 277, 44300-44309.  
11711606 C.W.Peng, V.V.Peremyslov, A.R.Mushegian, W.O.Dawson, and V.V.Dolja (2001).
Functional specialization and evolution of leader proteinases in the family Closteroviridae.
  J Virol, 75, 12153-12160.  
11356957 J.Chinsangaram, M.Koster, and M.J.Grubman (2001).
Inhibition of L-deleted foot-and-mouth disease virus replication by alpha/beta interferon involves double-stranded RNA-dependent protein kinase.
  J Virol, 75, 5498-5503.  
10933699 A.Kanjanahaluethai, and S.C.Baker (2000).
Identification of mouse hepatitis virus papain-like proteinase 2 activity.
  J Virol, 74, 7911-7921.  
11000252 C.W.Peng, and V.V.Dolja (2000).
Leader proteinase of the beet yellows closterovirus: mutation analysis of the function in genome amplification.
  J Virol, 74, 9766-9770.  
10681429 T.F.Kagawa, J.C.Cooney, H.M.Baker, S.McSweeney, M.Liu, S.Gubba, J.M.Musser, and E.N.Baker (2000).
Crystal structure of the zymogen form of the group A Streptococcus virulence factor SpeB: an integrin-binding cysteine protease.
  Proc Natl Acad Sci U S A, 97, 2235-2240.
PDB code: 1dki
10823845 Y.Liang, J.Yao, and S.Gillam (2000).
Rubella virus nonstructural protein protease domains involved in trans- and cis-cleavage activities.
  J Virol, 74, 5412-5423.  
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
10329692 J.Herold, S.G.Siddell, and A.E.Gorbalenya (1999).
A human RNA viral cysteine proteinase that depends upon a unique Zn2+-binding finger connecting the two domains of a papain-like fold .
  J Biol Chem, 274, 14918-14925.  
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.