User:Wayne Decatur/Haloarcula Large Ribosomal Subunit With Azithromycin: Difference between revisions

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Azithromycin is a 15-membered macrolide [http://en.wikipedia.org/wiki/Antibiotic antibiotic]. The structure of this cliniclally important antibiotic has been solved bound to the ''Haloarcula marismortui'' large ribosomal subunit revealing its mode of inhibiting protein synthesis<ref>PMID: 12150912</ref><ref>PMID: 15851032</ref>.
[http://en.wikipedia.org/wiki/Azithromycin Azithromycin] is a 15-membered macrolide [http://en.wikipedia.org/wiki/Antibiotic antibiotic] of the azalide subclass. The structure of this clinically important antibiotic has been solved bound to the ''Haloarcula marismortui'' large ribosomal subunit revealing its mode of inhibiting protein synthesis<ref>PMID: 12150912</ref><ref>PMID: 15851032</ref>.


The basic details of the [[User:Wayne Decatur/Haloarcula Large Ribosomal Subunit|''Haloarcula marismortui'' large ribosomal]] subunit are described in '''[[User:Wayne Decatur/Haloarcula Large Ribosomal Subunit|its own entry]]'''.
The basic details of the [[Large Ribosomal Subunit of Haloarcula|''Haloarcula marismortui'' large ribosomal]] subunit are described in '''[[Large Ribosomal Subunit of Haloarcula|its own entry]]''' while the structure of azithromycin (zithromax) and its interaction with the [[ribosome]] are shown below on this page.


==Mechanism of action==
==Mechanism of action==
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| <applet load='Azithromycin.pdb‎' size='390' frame='true' align='left' scene='User:Wayne_Decatur/Sandbox_Haloarcula_Large_Ribosomal_Subunit_With_Azithromycin/Azithromycin/2' />
| <applet load='Azithromycin.pdb‎' size='390' frame='true' align='left' scene='User:Wayne_Decatur/Sandbox_Haloarcula_Large_Ribosomal_Subunit_With_Azithromycin/Azithromycin/2' />
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|<table width='410' align='left' cellpadding='5'><tr><td rowspan='2'>&nbsp;</td><td bgcolor='#eeeeee'><applet load='1m1kalphac.pdb.gz' size='410' frame='true' align='right' scene='User:Wayne_Decatur/Sandbox_Haloarcula_Large_Ribosomal_Subunit_With_Azithromycin/1m1kazo/2' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Azithromycin bound to the Large Ribosomal Subunit''' ([[1m1k]]), resolution 3.2&Aring; (<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Large_Ribosomal_Subunit_With_Azithromycin/1m1kazo/2>initial scene</scene>). <br>
|<table width='410' align='left' cellpadding='5'><tr><td rowspan='2'>&nbsp;</td><td bgcolor='#eeeeee'><applet load='1m1kalphac.pdb.gz' size='410' frame='true' align='right' scene='User:Wayne_Decatur/Sandbox_Haloarcula_Large_Ribosomal_Subunit_With_Azithromycin/1m1kazo/2' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Azithromycin bound to the Large Ribosomal Subunit''' ([[1m1k]]), resolution 3.2&Aring; (<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Large_Ribosomal_Subunit_With_Azithromycin/1m1kazo/2'>initial scene</scene>). <br>
·· {{Link Toggle halolsuriborRNAb}} ·· {{Link Toggle halolsu23SrRNAb}} ·· {{Link Toggle halolsu5SrRNAb}} ··<br>·· {{Link Toggle 70SriboProtein}} ·· {{Link Toggle BlackWhiteBackground}}  ··</center></td></tr></table>
·· {{Link Toggle halolsuriborRNAb}} ·· {{Link Toggle halolsu23SrRNAb}} ·· {{Link Toggle halolsu5SrRNAb}} ··<br>·· {{Link Toggle 70SriboProtein}} ·· {{Link Toggle BlackWhiteBackground}}  ··</center></td></tr></table>
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<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Large_Ribosomal_Subunit_With_Azithromycin/1m1kazo/4'>Azithromycin sits in the tunnel where it would occlude the nascent polypeptide chain from transiting through the subunit</scene>.
<scene name='User:Wayne_Decatur/Sandbox_Haloarcula_Large_Ribosomal_Subunit_With_Azithromycin/1m1kazo/4'>Azithromycin sits in the tunnel where it would occlude the nascent polypeptide chain from transiting through the subunit</scene>.


'''Summary: Azithromycin, like other macrolides, binds in [[User:Wayne Decatur/Haloarcula Large Ribosomal Subunit#Polypeptide Exit Tunnel:|the polypeptide exit tunnel]] near its start [[User:Wayne Decatur/Haloarcula Large Ribosomal Subunit#Polypeptide Exit Tunnel:|the polypeptide exit tunnel]] inhibiting protein synthesis by blocking the progression of nascent polypeptides through the tunnel.''' '''[[User:Wayne Decatur/Haloarcula Large Ribosomal Subunit#Polypeptide Exit Tunnel:|The polypeptide exit tunnel]]''' is described '''[[User:Wayne Decatur/Haloarcula Large Ribosomal Subunit#Polypeptide Exit Tunnel:|here]]'''.
'''Summary: Azithromycin, like other macrolides, binds in [[Large Ribosomal Subunit of Haloarcula#Polypeptide Exit Tunnel:|the polypeptide exit tunnel]] near its start [[Large Ribosomal Subunit of Haloarcula#Polypeptide Exit Tunnel:|the polypeptide exit tunnel]] inhibiting protein synthesis by blocking the progression of nascent polypeptides through the tunnel.''' '''[[Large Ribosomal Subunit of Haloarcula#Polypeptide Exit Tunnel:|The polypeptide exit tunnel]]''' is described '''[[Large Ribosomal Subunit of Haloarcula#Polypeptide Exit Tunnel:|here]]'''.


==About this Structure==
==About this Structure==
[[1m1k]] is a 30 chains structure of sequences from [http://en.wikipedia.org/wiki/Haloarcula_marismortui Haloarcula marismortui]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M1K OCA]. A version of [[1m1k]] optimized for use online as described [[User:Wayne Decatur/SandboxRibosome&Antibiotics|here]] is used on this page. You may wish to examine the [[User:Wayne Decatur/Haloarcula Large Ribosomal Subunit|basics of the subunit]].
[[1m1k]] is a 30 chains structure of sequences from [http://en.wikipedia.org/wiki/Haloarcula_marismortui Haloarcula marismortui]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M1K OCA]. A version of [[1m1k]] optimized for use online as described [[User:Wayne Decatur/Interactions between Antibiotics and the Ribosome|here]] is used on this page. You may wish to examine the [[Large Ribosomal Subunit of Haloarcula|basics of the subunit]].


==Reference for the Structure==
==Reference for the Structure==
<ref group="xtra">PMID:12150912</ref><references group="xtra"/>
<ref group="xtra">PMID: 12150912</ref><references group="xtra"/>


==Related Structures==
==Related Structures==
*[[User:Wayne Decatur/Haloarcula Large Ribosomal Subunit|Haloarcula Large Ribosomal Subunit]]
*[[Large Ribosomal Subunit of Haloarcula|Haloarcula Large Ribosomal Subunit]]
*[[User:Wayne Decatur/Interactions between Antibiotics and the Ribosome|Interactions between Antibiotics and the Ribosome]]
*[[1nwy]] The Large Ribosomal Subunit From ''Deinococcus radiodurans'' complexed with Azithromycin<ref>PMID: 12623020</ref>  
*[[1nwy]] The Large Ribosomal Subunit From ''Deinococcus radiodurans'' complexed with Azithromycin<ref>PMID: 12623020</ref>  
*[[1yhq]] ''Haloarcula marismortui'' large ribosomal subunit containing the mutation G2099A (A2058 in ''E. coli'') complexed with Azithromycin - despite the change to the eubacterial-like adenosine at this position azithromycin binds essentially the same way to either Haloarcula subunit<ref>PMID: 15851032</ref>
*[[1yhq]] ''Haloarcula marismortui'' large ribosomal subunit containing the mutation G2099A (A2058 in ''E. coli'') complexed with Azithromycin - despite the change to the eubacterial-like adenosine at this position azithromycin binds essentially the same way to either Haloarcula subunit<ref>PMID: 15851032</ref>
*[[1kd1]] The Large Ribosomal Subunit From ''H. marismortui'' complexed with the 16-membered macrolide spiramycin<ref>PMID: PMID:12150912</ref>
*[[1kd1]] The Large Ribosomal Subunit From ''H. marismortui'' complexed with the 16-membered macrolide spiramycin<ref>PMID: 12150912</ref>
*[[1k9m]] The Large Ribosomal Subunit From ''H. marismortui'' complexed with the 16-membered macrolide Tylosin<ref>PMID: PMID:12150912</ref>
*[[1k9m]] The Large Ribosomal Subunit From ''H. marismortui'' complexed with the 16-membered macrolide Tylosin<ref>PMID: 12150912</ref>
*[[1k8a]] The Large Ribosomal Subunit From ''H. marismortui'' complexed with the 16-membered macrolide Carbomycin A<ref>PMID: PMID:12150912</ref>
*[[1k8a]] The Large Ribosomal Subunit From ''H. marismortui'' complexed with the 16-membered macrolide Carbomycin A<ref>PMID: 12150912</ref>
 
*[[3cc2]] The refined structure of the Large Ribosomal Subunit From ''H. marismortui''<ref>PMID: 18455733</ref>


==References==
==References==
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==Additional Literature and Resources==
==Additional Literature and Resources==
<ref group="xtra">PMID: 18382121</ref><ref group="xtra">PMID: 15680981</ref>
<ref group="xtra">PMID: 18382121</ref><ref group="xtra">PMID: 15680981</ref><references group="xtra"/>  
<references group="xtra"/>  
*[http://www.drugbank.ca/drugs/DB00207 Azithromycin at the DrugBank database]
*[http://www.drugbank.ca/drugs/DB00207 Azithromycin at the DrugBank database]
*[http://www.drugs.com/zithromax.html Azithromycin (zithromax) at Drugs.com]
*[http://www.drugs.com/zithromax.html Azithromycin (zithromax) at Drugs.com]
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[[Category: Nissen, P.]]
[[Category: Nissen, P.]]
[[Category: Steitz, T A.]]
[[Category: Steitz, T A.]]
[[Category: 50]]
[[Category: Azithromycin]]
[[Category: Azithromycin]]
[[Category: Zithromax]]
[[Category: Zithromax]]
[[Category: Haloarcula]]
[[Category: Haloarcula]]
[[Category: Macrolide]]
[[Category: Macrolide]]
[[Category: Azalide]]
[[Category: Antibiotic]]
[[Category: Antibiotic]]
[[Category: 50S]]
[[Category: 50S]]
[[Category: Large ribosomal subunit]]
[[Category: Large ribosomal subunit]]
[[Category: Ribosome]]
[[Category: Ribosome]]