1vbc

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(New page: 200px<br /><applet load="1vbc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vbc, resolution 2.8&Aring;" /> '''POLIOVIRUS (TYPE 3, S...)
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[[Image:1vbc.gif|left|200px]]<br /><applet load="1vbc" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1vbc, resolution 2.8&Aring;" />
caption="1vbc, resolution 2.8&Aring;" />
'''POLIOVIRUS (TYPE 3, SABIN STRAIN) (P3/SABIN, P3/LEON/12A(1)B) COMPLEXED WITH R77975'''<br />
'''POLIOVIRUS (TYPE 3, SABIN STRAIN) (P3/SABIN, P3/LEON/12A(1)B) COMPLEXED WITH R77975'''<br />
==Overview==
==Overview==
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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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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.
==About this Structure==
==About this Structure==
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1VBC is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Viruses Viruses] with MYR and J77 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1VBC OCA].
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1VBC is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Viruses Viruses] with <scene name='pdbligand=MYR:'>MYR</scene> and <scene name='pdbligand=J77:'>J77</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VBC OCA].
==Reference==
==Reference==
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[[Category: Viruses]]
[[Category: Viruses]]
[[Category: Andries, K.]]
[[Category: Andries, K.]]
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[[Category: Filman, D.J.]]
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[[Category: Filman, D J.]]
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[[Category: Grant, R.A.]]
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[[Category: Grant, R A.]]
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[[Category: Hiremath, C.N.]]
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[[Category: Hiremath, C N.]]
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[[Category: Hogle, J.M.]]
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[[Category: Hogle, J M.]]
[[Category: Syed, R.]]
[[Category: Syed, R.]]
[[Category: J77]]
[[Category: J77]]
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[[Category: virus coat protein]]
[[Category: virus coat protein]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 04:34:13 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:33:26 2008''

Revision as of 13:33, 21 February 2008

Image:1vbc.gif

1vbc, resolution 2.8Å

Drag the structure with the mouse to rotate

POLIOVIRUS (TYPE 3, SABIN STRAIN) (P3/SABIN, P3/LEON/12A(1)B) COMPLEXED WITH R77975

Overview

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.

About this Structure

1VBC is a Protein complex structure of sequences from Viruses with and as ligands. Full crystallographic information is available from OCA.

Reference

Structures of poliovirus complexes with anti-viral drugs: implications for viral stability and drug design., Grant RA, Hiremath CN, Filman DJ, Syed R, Andries K, Hogle JM, Curr Biol. 1994 Sep 1;4(9):784-97. PMID:7820548

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