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PDBsum entry 1vbc
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279 a.a.
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266 a.a.
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235 a.a.
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62 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structures of poliovirus complexes with anti-Viral drugs: implications for viral stability and drug design.
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Authors
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R.A.Grant,
C.N.Hiremath,
D.J.Filman,
R.Syed,
K.Andries,
J.M.Hogle.
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Ref.
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Curr Biol, 1994,
4,
784-797.
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PubMed id
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Abstract
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BACKGROUND: Picornaviruses, such as the structurally related polioviruses and
rhinoviruses, are important human pathogens which have been the target of major
drug development efforts. Receptor-mediated uncoating and thermal inactivation
of poliovirus and rhinovirus are inhibited by agents that bind to each virus by
inserting into a pocket in the beta barrel of the viral capsid protein, VP1.
This pocket, which is normally empty in human rhinovirus-14 (HRV14), is occupied
by an unknown natural ligand in poliovirus. Structural studies of HRV14-drug
complexes have shown that drug binding causes large, localized changes in the
conformation of VP1. RESULTS: We report the crystal structures of six complexes
between poliovirus and capsid-binding, antiviral drugs, including complexes of
four different drugs with the Sabin vaccine strain of type 3 poliovirus, and
complexes of one of these drugs with two other poliovirus strains that contain
sequence differences in the drug-binding site. In each complex, the changes in
capsid structure associated with drug binding are limited to minor adjustments
in the conformations of a few side chains lining the binding site. CONCLUSIONS:
The minor structural changes caused by drug binding suggest a model of drug
action in which it is the conformational changes prevented by the bound drug,
rather than obvious conformational changes induced by drug binding, which exert
the biological effect. Our results, along with additional structures of
rhinovirus-drug complexes, suggest possible improvements in drug design, and
provide important clues about the nature of the conformational changes that are
involved in the uncoating process.
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Secondary reference #1
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Title
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Binding of the antiviral drug win51711 to the sabin strain of type 3 poliovirus: structural comparison with drug binding in rhinovirus 14.
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Authors
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C.N.Hiremath,
R.A.Grant,
D.J.Filman,
J.M.Hogle.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 1995,
51,
473-489.
[DOI no: ]
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PubMed id
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Figure 6.
Fig. 6. The ability of 15fold noncrystallographic ymmetry constraints to minimize te effects of deliberate model bias in the P3/Sabin complex
with WIN5171. As explained in he text, a substantially correct atomic model of the complex, with the isoxazole group of WIN51711 located
in the outer pocket, was use to initiate phasing in the refinement that produced the electrondensity maps show in (a) and (b). An incorrect
model of the drug, shown in pink, with its isoxazole group ocated at the uried end of the pocket, was used to initiate phase refinement for the
maps i (c) and (d). For greater cla{i.'ty, portions of the map and model at the front and back of these views have been truncated and portions
of the atomic model further than 7 A from the drug have been omitted. (a) and (c) are side views of the pocket, seen from viewponts similar
to Fig 5 (a). (b) and (d) are top views, see from viewponts similar to Fig. 5(b).
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Figure 7.
Fig. 7. Stereoview of the unbiased electrondensity map in the vicinity
of Ile1183 in the P3/Sabin complex with WIN51711. The calculation
of this map is expained in the text. This is a side view, similr in
viewpoint to Fig. 5(a). Electron density for the bound oxazoline group
is visible at the bottom of te picture. The atomic coordinates shown
in purple represent the conformation of I1e1183 in the structure of
native P3/Sabin and the rest of the coordinates belong to te model
of the drugvirus complex. Note that the native conformation of the
Ile1183 side chain would be in steric conlict with the oxazoline ring.
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The above figures are
reproduced from the cited reference
with permission from the IUCr
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Secondary reference #2
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Title
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Role of conformational transitions in poliovirus assembly and cell entry
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Authors
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J.M.Hogle,
R.Syed,
C.E.Fricks,
J.P.Icenogle,
O.Flore,
D.J.Filman.
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Ref.
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new aspects of ...
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Secondary reference #3
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Title
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Structural factors that control conformational transitions and serotype specificity in type 3 poliovirus.
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Authors
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D.J.Filman,
R.Syed,
M.Chow,
A.J.Macadam,
P.D.Minor,
J.M.Hogle.
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Ref.
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Embo J, 1989,
8,
1567-1579.
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PubMed id
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Secondary reference #4
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Title
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Myristylation of picornavirus capsid protein vp4 and its structural significance.
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Authors
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M.Chow,
J.F.Newman,
D.Filman,
J.M.Hogle,
D.J.Rowlands,
F.Brown.
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Ref.
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Nature, 1987,
327,
482-486.
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PubMed id
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Secondary reference #5
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Title
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Three-Dimensional structure of poliovirus at 2.9 a resolution.
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Authors
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J.M.Hogle,
M.Chow,
D.J.Filman.
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Ref.
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Science, 1985,
229,
1358-1365.
[DOI no: ]
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PubMed id
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Secondary reference #6
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Title
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The nucleotide sequence of poliovirus type 3 leon 12 a1b: comparison with poliovirus type 1.
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Authors
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G.Stanway,
A.J.Cann,
R.Hauptmann,
P.Hughes,
L.D.Clarke,
R.C.Mountford,
P.D.Minor,
G.C.Schild,
J.W.Almond.
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Ref.
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Nucleic Acids Res, 1983,
11,
5629-5643.
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PubMed id
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