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PDBsum entry 1qjx

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protein ligands metals Protein-protein interface(s) links
Virus PDB id
1qjx
Jmol
Contents
Protein chains
285 a.a. *
252 a.a. *
238 a.a. *
29 a.a. *
Ligands
W02
MYR
Metals
_ZN
Waters ×270
* Residue conservation analysis
PDB id:
1qjx
Name: Virus
Title: Human rhinovirus 16 coat protein in complex with antiviral compound win68934
Structure: Protein vp1. Chain: 1. Fragment: residues 569-853. Synonym: virion protein 1, p1d, human rhinovirus 16 coat protein. Protein vp2. Chain: 2. Fragment: residues 70-330. Synonym: virion protein 2, p1b, human rhinovirus 16 coat
Source: Human rhinovirus 16. Hrv-16. Organism_taxid: 31708. Strain: serotype 16. Strain: serotype 16
Resolution:
2.80Å     R-factor:   0.231     R-free:   0.235
Authors: A.T.Hadfield,G.D.Diana,M.G.Rossmann
Key ref:
A.T.Hadfield et al. (1999). Analysis of three structurally related antiviral compounds in complex with human rhinovirus 16. Proc Natl Acad Sci U S A, 96, 14730-14735. PubMed id: 10611281 DOI: 10.1073/pnas.96.26.14730
Date:
06-Jul-99     Release date:   20-Jul-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q82122  (POLG_HRV16) -  Genome polyprotein
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2153 a.a.
285 a.a.
Protein chain
Pfam   ArchSchema ?
Q82122  (POLG_HRV16) -  Genome polyprotein
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2153 a.a.
252 a.a.
Protein chain
Pfam   ArchSchema ?
Q82122  (POLG_HRV16) -  Genome polyprotein
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2153 a.a.
238 a.a.
Protein chain
Pfam   ArchSchema ?
Q82122  (POLG_HRV16) -  Genome polyprotein
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2153 a.a.
29 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: Chains 1, 2, 3, 4: 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: Chains 1, 2, 3, 4: 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: Chains 1, 2, 3, 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: Chains 1, 2, 3, 4: 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!
  Cellular component     viral capsid   1 term 
  Biochemical function     structural molecule activity     1 term  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.96.26.14730 Proc Natl Acad Sci U S A 96:14730-14735 (1999)
PubMed id: 10611281  
 
 
Analysis of three structurally related antiviral compounds in complex with human rhinovirus 16.
A.T.Hadfield, G.D.Diana, M.G.Rossmann.
 
  ABSTRACT  
 
Rhinoviruses are a frequent cause of the common cold. A series of antirhinoviral compounds have been developed that bind into a hydrophobic pocket in the viral capsid, stabilizing the capsid and interfering with cell attachment. The structures of a variety of such compounds, complexed with rhinovirus serotypes 14, 16, 1A, and 3, previously have been examined. Three chemically similar compounds, closely related to a drug that is undergoing phase III clinical trials, were chosen to determine the structural impact of the heteroatoms in one of the three rings. The compounds were found to have binding modes that depend on their electronic distribution. In the compound with the lowest efficacy, the terminal ring is displaced by 1 A and rotated by 180 degrees relative to the structure of the other two. The greater polarity of the terminal ring in one of the three compounds leads to a small displacement of its position relative to the other compounds in the hydrophobic end of the antiviral compound binding pocket to a site where it makes fewer interactions. Its lower efficacy is likely to be the result of the reduced number of interactions. A region of conserved residues has been identified near the entrance to the binding pocket where there is a corresponding conservation of the mode of binding of these compounds to different serotypes. Thus, variations in residues lining the more hydrophobic end of the pocket are primarily responsible for the differences in drug efficacies.
 
  Selected figure(s)  
 
Figure 4.
Fig. 4. Difference in binding of compounds 1 and 2 compared with compound 3. (A) Electron density for compound 1, contoured at a 1.5 level. Compound 1 is shown in purple bonds and compound 3 is shown as black bonds. (B) Ball-and-stick representation of compound 1 (black sticks) and compound 3 (green sticks) viewed from (Lower) looking from the compound toward the outside of the virion and (Upper) looking from the compound toward the center of the virion. The insert localizes the site with respect to the symmetry axes in the icosahedral asymmetric unit. The labels X and Y define opposite sides of the WIN binding pocket. Side chains that are within 4 Å of the compounds are shown in thin black bonds. Water molecules are shown as red spheres with their hydrogen bonding environment in ball-and-stick representation. Compound 4 is overlaid in green dotted lines. The figure was prepared by using MOLSCRIPT (43).
Figure 5.
Fig. 5. The same as Fig. 4B, but showing the comparison of compound binding sites in HRV16 and HRV14. Ball-and-stick representation of compound 1 (white sticks) bound to HRV16 (side chains within 4 Å shown in thin black bonds). The binding pocket of HRV14 with two compounds bound is superimposed. Compound 5 is shown in black ball-and-stick representation, while compound 6 is shown as dashed magenta lines (side chains within 4 Å of the compounds shown in magenta bonds). The comparison is based on a least-squares fit between C[ ]atoms in the -barrel of VP1.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19714577 J.M.Rollinger, and M.Schmidtke (2011).
The human rhinovirus: human-pathological impact, mechanisms of antirhinoviral agents, and strategies for their discovery.
  Med Res Rev, 31, 42-92.  
18585795 R.Perera, M.Khaliq, and R.J.Kuhn (2008).
Closing the door on flaviviruses: entry as a target for antiviral drug design.
  Antiviral Res, 80, 11-22.  
18498137 V.L.Morton, P.G.Stockley, N.J.Stonehouse, and A.E.Ashcroft (2008).
Insights into virus capsid assembly from non-covalent mass spectrometry.
  Mass Spectrom Rev, 27, 575-595.  
19033206 Y.Modis (2008).
How influenza virus is locked out of the cell.
  Proc Natl Acad Sci U S A, 105, 18647-18648.  
17334823 K.H.Kim (2007).
Outliers in SAR and QSAR: is unusual binding mode a possible source of outliers?
  J Comput Aided Mol Des, 21, 63-86.  
17161425 R.B.Gonçalves, Y.S.Mendes, M.R.Soares, U.Katpally, T.J.Smith, J.L.Silva, and A.C.Oliveira (2007).
VP4 protein from human rhinovirus 14 is released by pressure and locked in the capsid by the antiviral compound WIN.
  J Mol Biol, 366, 295-306.  
17009092 T.M.Steindl, D.Schuster, G.Wolber, C.Laggner, and T.Langer (2006).
High-throughput structure-based pharmacophore modelling as a basis for successful parallel virtual screening.
  J Comput Aided Mol Des, 20, 703-715.  
15596823 T.C.Appleby, H.Luecke, J.H.Shim, J.Z.Wu, I.W.Cheney, W.Zhong, L.Vogeley, Z.Hong, and N.Yao (2005).
Crystal structure of complete rhinovirus RNA polymerase suggests front loading of protein primer.
  J Virol, 79, 277-288.
PDB code: 1tp7
15452226 Y.Zhang, A.A.Simpson, R.M.Ledford, C.M.Bator, S.Chakravarty, G.A.Skochko, T.M.Demenczuk, A.Watanyar, D.C.Pevear, and M.G.Rossmann (2004).
Structural and virological studies of the stages of virus replication that are affected by antirhinovirus compounds.
  J Virol, 78, 11061-11069.
PDB codes: 1na1 1ncq 1ncr 1nd2 1nd3
14624862 A.Zlotnick, and S.J.Stray (2003).
How does your virus grow? Understanding and interfering with virus assembly.
  Trends Biotechnol, 21, 536-542.  
12802751 F.G.Hayden, D.T.Herrington, T.L.Coats, K.Kim, E.C.Cooper, S.A.Villano, S.Liu, S.Hudson, D.C.Pevear, M.Collett, and M.McKinlay (2003).
Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials.
  Clin Infect Dis, 36, 1523-1532.  
12828863 M.Yamaya, and H.Sasaki (2003).
Rhinovirus and asthma.
  Viral Immunol, 16, 99.  
12233786 M.Yamaya (2002).
Pathogenesis and management of virus infection-induced exacerbation of senile bronchial asthma and chronic pulmonary emphysema.
  Tohoku J Exp Med, 197, 67-80.  
11178348 J.R.Romero (2001).
Pleconaril: a novel antipicornaviral drug.
  Expert Opin Investig Drugs, 10, 369-379.  
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.