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273 a.a.
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255 a.a.
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236 a.a.
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40 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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Structural studies on human rhinovirus 14 drug-Resistant compensation mutants.
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Authors
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A.T.Hadfield,
M.A.Oliveira,
K.H.Kim,
I.Minor,
M.J.Kremer,
B.A.Heinz,
D.Shepard,
D.C.Pevear,
R.R.Rueckert,
M.G.Rossmann.
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Ref.
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J Mol Biol, 1995,
253,
61-73.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
90%.
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Abstract
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Structures have been determined of three human rhinovirus 14 (HRV14)
compensation mutants that have resistance to the antiviral capsid binding
compounds WIN 52035 and WIN 52084. In addition, the structure of HRV14 is
reported, with a site-directed mutation at residue 1219 in VP1. A spontaneous
mutation occurs at the same site in one of the compensation mutants. Some of the
mutations are on the viral surface in the canyon and some lie within the
hydrophobic binding pocket in VP1 below the ICAM footprint. Those mutant virus
strains with mutations on the surface bind better to cells than does wild-type
virus. The antiviral compounds bind to the mutant viruses in a manner similar to
their binding to wild-type virus. The receptor and WIN compound binding sites
overlap, causing competition between receptor attachment and antiviral compound
binding. The compensation mutants probably function by shifting the equilibrium
in favor of receptor binding. The mutations in the canyon increase the affinity
of the virus for the receptor, while the mutations in the pocket probably
decrease the affinity of the WIN compounds for the virus by reducing favorable
hydrophobic contacts and constricting the pore through which the antiviral
compounds are thought to enter the pocket. This is in contrast to the resistant
exclusion mutants that block compounds from binding by increasing the bulk of
residues within the hydrophobic pocket in VP1.
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Secondary reference #1
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Title
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Win 52035-2 inhibits both attachment and eclipse of human rhinovirus 14.
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Authors
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D.A.Shepard,
B.A.Heinz,
R.R.Rueckert.
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Ref.
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J Virol, 1993,
67,
2245-2254.
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PubMed id
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Secondary reference #2
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Title
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Analysis of the structure of a common cold virus, Human rhinovirus 14, Refined at a resolution of 3.0 a.
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Authors
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E.Arnold,
M.G.Rossmann.
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Ref.
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J Mol Biol, 1990,
211,
763-801.
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PubMed id
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Secondary reference #3
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Title
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Three-Dimensional structures of drug-Resistant mutants of human rhinovirus 14.
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Authors
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J.Badger,
S.Krishnaswamy,
M.J.Kremer,
M.A.Oliveira,
M.G.Rossmann,
B.A.Heinz,
R.R.Rueckert,
F.J.Dutko,
M.A.Mckinlay.
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Ref.
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J Mol Biol, 1989,
207,
163-174.
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PubMed id
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Secondary reference #4
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Title
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Structural analysis of antiviral agents that interact with the capsid of human rhinoviruses.
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Authors
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J.Badger,
I.Minor,
M.A.Oliveira,
T.J.Smith,
M.G.Rossmann.
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Ref.
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Proteins, 1989,
6,
1.
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PubMed id
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Secondary reference #5
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Title
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Genetic and molecular analyses of spontaneous mutants of human rhinovirus 14 that are resistant to an antiviral compound.
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Authors
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B.A.Heinz,
R.R.Rueckert,
D.A.Shepard,
F.J.Dutko,
M.A.Mckinlay,
M.Fancher,
M.G.Rossmann,
J.Badger,
T.J.Smith.
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Ref.
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J Virol, 1989,
63,
2476-2485.
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PubMed id
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Secondary reference #6
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Title
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The use of molecular-Replacement phases for the refinement of the human rhinovirus 14 structure.
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Authors
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E.Arnold,
M.G.Rossmann.
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Ref.
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Acta Crystallogr A, 1988,
44,
270-282.
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PubMed id
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Secondary reference #7
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Title
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Structural analysis of a series of antiviral agents complexed with human rhinovirus 14.
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Authors
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J.Badger,
I.Minor,
M.J.Kremer,
M.A.Oliveira,
T.J.Smith,
J.P.Griffith,
D.M.Guerin,
S.Krishnaswamy,
M.Luo,
M.G.Rossmann.
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Ref.
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Proc Natl Acad Sci U S A, 1988,
85,
3304-3308.
[DOI no: ]
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PubMed id
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Secondary reference #8
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Title
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The structure determination of a common cold virus, Human rhinovirus 14
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Authors
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E.Arnold,
G.Vriend,
M.Luo,
J.P.Griffith,
G.Kamer,
J.W.Erickson,
J.E.Johnson,
M.G.Rossmann.
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Ref.
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acta crystallogr ,sect a, 1987,
43,
346.
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Secondary reference #9
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Title
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The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating.
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Authors
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T.J.Smith,
M.J.Kremer,
M.Luo,
G.Vriend,
E.Arnold,
G.Kamer,
M.G.Rossmann,
M.A.Mckinlay,
G.D.Diana,
M.J.Otto.
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Ref.
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Science, 1986,
233,
1286-1293.
[DOI no: ]
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PubMed id
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Secondary reference #10
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Title
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Structure of a human common cold virus and functional relationship to other picornaviruses.
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Authors
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M.G.Rossmann,
E.Arnold,
J.W.Erickson,
E.A.Frankenberger,
J.P.Griffith,
H.J.Hecht,
J.E.Johnson,
G.Kamer,
M.Luo,
A.G.Mosser.
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Ref.
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Nature, 1985,
317,
145-153.
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PubMed id
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Secondary reference #11
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Title
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Virion orientation in cubic crystals of the human common cold virus hrv14.
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Authors
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E.Arnold,
J.W.Erickson,
G.S.Fout,
E.A.Frankenberger,
H.J.Hecht,
M.Luo,
M.G.Rossman,
R.R.Rueckert.
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Ref.
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J Mol Biol, 1984,
177,
417-430.
[DOI no: ]
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PubMed id
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Figure 1.
Fro. 1. Cubic RlP rystals in a hanging drop within a vapor diffusion well. The prncipal faces of the
csrystals correspond to octahedral geometry. These crystals were approximately 0.3 mm in diameter.
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Figure 3.
Fro. 3. Stereographic projction illustrating the data collection scheme
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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