1ruf
From Proteopedia
(New page: 200px<br /><applet load="1ruf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ruf, resolution 2.9Å" /> '''RHINOVIRUS 14 (HRV14)...) |
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| - | [[Image:1ruf.gif|left|200px]]<br /><applet load="1ruf" size=" | + | [[Image:1ruf.gif|left|200px]]<br /><applet load="1ruf" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ruf, resolution 2.9Å" /> | caption="1ruf, resolution 2.9Å" /> | ||
'''RHINOVIRUS 14 (HRV14) (MUTANT WITH ASN 1 219 REPLACED BY ALA (N219A IN CHAIN 1)'''<br /> | '''RHINOVIRUS 14 (HRV14) (MUTANT WITH ASN 1 219 REPLACED BY ALA (N219A IN CHAIN 1)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Structures have been determined of three human rhinovirus 14 (HRV14) | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1RUF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_rhinovirus_10 Human rhinovirus 10]. Full crystallographic information is available from [http:// | + | 1RUF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_rhinovirus_10 Human rhinovirus 10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RUF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Hadfield, A.]] | [[Category: Hadfield, A.]] | ||
| - | [[Category: Heinz, B | + | [[Category: Heinz, B A.]] |
| - | [[Category: Kim, K | + | [[Category: Kim, K H.]] |
| - | [[Category: Kremer, M | + | [[Category: Kremer, M J.]] |
[[Category: Minor, I.]] | [[Category: Minor, I.]] | ||
| - | [[Category: Oliveira, M | + | [[Category: Oliveira, M A.]] |
| - | [[Category: Pevear, D | + | [[Category: Pevear, D C.]] |
| - | [[Category: Rossmann, M | + | [[Category: Rossmann, M G.]] |
| - | [[Category: Rueckert, R | + | [[Category: Rueckert, R R.]] |
[[Category: Shepard, D.]] | [[Category: Shepard, D.]] | ||
[[Category: icosahedral virus]] | [[Category: icosahedral virus]] | ||
[[Category: rhinovirus coat protein]] | [[Category: rhinovirus coat protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:54:47 2008'' |
Revision as of 12:54, 21 February 2008
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RHINOVIRUS 14 (HRV14) (MUTANT WITH ASN 1 219 REPLACED BY ALA (N219A IN CHAIN 1)
Overview
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.
About this Structure
1RUF is a Single protein structure of sequence from Human rhinovirus 10. Full crystallographic information is available from OCA.
Reference
Structural studies on human rhinovirus 14 drug-resistant compensation mutants., Hadfield AT, Oliveira MA, Kim KH, Minor I, Kremer MJ, Heinz BA, Shepard D, Pevear DC, Rueckert RR, Rossmann MG, J Mol Biol. 1995 Oct 13;253(1):61-73. PMID:7473717
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