1hrv
From Proteopedia
(New page: 200px<br /><applet load="1hrv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hrv, resolution 3.Å" /> '''HRV14/SDZ 35-682 COMPL...) |
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| - | [[Image:1hrv.jpg|left|200px]]<br /><applet load="1hrv" size=" | + | [[Image:1hrv.jpg|left|200px]]<br /><applet load="1hrv" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1hrv, resolution 3.Å" /> | caption="1hrv, resolution 3.Å" /> | ||
'''HRV14/SDZ 35-682 COMPLEX'''<br /> | '''HRV14/SDZ 35-682 COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | SDZ 35-682 is a potent and selective inhibitor of the replication of | + | SDZ 35-682 is a potent and selective inhibitor of the replication of members of the picornavirus group. It inhibits several rhinovirus serotypes and echovirus 9 at concentrations as low as 0.1 micrograms/ml, without exerting any effect on cell proliferation up to 30 micrograms/ml. As observed with other capsid-binding antipicornavirus compounds, there is a wide variation in sensitivity of the different serotypes within the rhinovirus group. The point of interference of SDZ 35-682 in a single cycle of virus growth is an early event taking place before 2 or 3 h of echo- or rhinovirus replication, respectively. By incorporation of neutral red into the viral capsid and measurement of acquisition of photoresistance it is shown that uncoating of echovirus 9 is inhibited by SDZ 35-682. In addition, efficiency of adsorption of echovirus 9 is reduced by SDZ 35-682. To demonstrate that SDZ 35-682, like other uncoating inhibitors of picornaviruses, binds to the hydrophobic pocket beneath the canyon floor co-crystallization with HRV 14 was performed. Considerable conformational changes occur in VP1 in the HRV 14/SDZ 35-682 complex. SDZ 35-682 is 19 A long from end to end and thus fills the entire hydrophobic pocket including its innermost end; it is less flexible than other long antiviral agents. It has been suggested that compounds filling the entire hydrophobic pocket will affect the uncoating process of the virion. Thus, inhibition of viral uncoating, as demonstrated with echovirus 9, probably is the predominant mode of action of SDZ 35-682. |
==About this Structure== | ==About this Structure== | ||
| - | 1HRV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_rhinovirus_10 Human rhinovirus 10] with SDZ as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1HRV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_rhinovirus_10 Human rhinovirus 10] with <scene name='pdbligand=SDZ:'>SDZ</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HRV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Arnold, E.]] | [[Category: Arnold, E.]] | ||
| - | [[Category: Oren, D | + | [[Category: Oren, D A.]] |
[[Category: Zhang, A.]] | [[Category: Zhang, A.]] | ||
[[Category: SDZ]] | [[Category: SDZ]] | ||
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[[Category: icosahedral virus]] | [[Category: icosahedral virus]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:04:19 2008'' |
Revision as of 11:04, 21 February 2008
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HRV14/SDZ 35-682 COMPLEX
Overview
SDZ 35-682 is a potent and selective inhibitor of the replication of members of the picornavirus group. It inhibits several rhinovirus serotypes and echovirus 9 at concentrations as low as 0.1 micrograms/ml, without exerting any effect on cell proliferation up to 30 micrograms/ml. As observed with other capsid-binding antipicornavirus compounds, there is a wide variation in sensitivity of the different serotypes within the rhinovirus group. The point of interference of SDZ 35-682 in a single cycle of virus growth is an early event taking place before 2 or 3 h of echo- or rhinovirus replication, respectively. By incorporation of neutral red into the viral capsid and measurement of acquisition of photoresistance it is shown that uncoating of echovirus 9 is inhibited by SDZ 35-682. In addition, efficiency of adsorption of echovirus 9 is reduced by SDZ 35-682. To demonstrate that SDZ 35-682, like other uncoating inhibitors of picornaviruses, binds to the hydrophobic pocket beneath the canyon floor co-crystallization with HRV 14 was performed. Considerable conformational changes occur in VP1 in the HRV 14/SDZ 35-682 complex. SDZ 35-682 is 19 A long from end to end and thus fills the entire hydrophobic pocket including its innermost end; it is less flexible than other long antiviral agents. It has been suggested that compounds filling the entire hydrophobic pocket will affect the uncoating process of the virion. Thus, inhibition of viral uncoating, as demonstrated with echovirus 9, probably is the predominant mode of action of SDZ 35-682.
About this Structure
1HRV is a Protein complex structure of sequences from Human rhinovirus 10 with as ligand. Full crystallographic information is available from OCA.
Reference
SDZ 35-682, a new picornavirus capsid-binding agent with potent antiviral activity., Rosenwirth B, Oren DA, Arnold E, Kis ZL, Eggers HJ, Antiviral Res. 1995 Jan;26(1):65-82. PMID:7741522
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