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Ribosome interactions with Paromomycin



==Mechanism of action==
{|
|-valign="top"
| <applet load='Paromomycinfrom2j00.pdb.gz' size='390' frame='true' align='left' scene='User:Wayne_Decatur/Sandbox_Thermus_70S_With_Paromomycin/Paromomycin/1' />
||
|<table width='410' align='left' cellpadding='5'><tr><td rowspan='2'>&nbsp;</td><td bgcolor='#eeeeee'><applet load='2j01and2j00andrestofAsitetRNAalphac.pdb.gz' size='410' frame='true' align='right' scene='User:Wayne_Decatur/Sandbox_Thermus_70S_With_Paromomycin/70swithparbest/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''REPLACE WITH PAROMOMYCN BOUND TO SMALL SUBUNIT'''<br>'''Paromomycin bound to the ribosome''' ([[2j01]] and [[2j00]]), resolution 2.8&Aring; (<scene name='User:Wayne_Decatur/Sandbox_Thermus_70S_With_Paromomycin/70swithparbest/1'>initial scene</scene>). <br>
·· {{Link Toggle halolsuriborRNAb}} ·· {{Link Toggle halolsu23SrRNAb}} ·· {{Link Toggle halolsu5SrRNAb}} ··<br>·· {{Link Toggle 70SriboProtein}} ·· {{Link Toggle BlackWhiteBackground}}  ··</center></td></tr></table>
|}

NEED TO DO STILL: SSU alone with PAR


Ramakrishnan one with Par

<table width='550' align='right' cellpadding='5'><tr><td rowspan='2'>&nbsp;</td><td bgcolor='#eeeeee'><applet load='2j01and2j00andrestofAsitetRNAalphac.pdb.gz' size='540' frame='true' align='right' scene='User:Wayne_Decatur/Sandbox_Thermus_70S_With_Paromomycin/70swithpar/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Paromomycin bound to the ribosome''' ([[2j01]] and [[2j00]]), resolution 2.8&Aring; (<scene name='User:Wayne_Decatur/Sandbox_Thermus_70S_With_Paromomycin/70swithpar/1'>initial scene</scene>). <br>
·· {{Link Toggle 70SselmerribotRNAs}} ·· {{Link Toggle 70SselmerribomRNA}} ·· {{Link Toggle 70SriborRNA}} ·· {{Link Toggle 70SriboProtein}} ··<br>
·· {{Link Toggle 70SselmerriboAsitetRNA}} ·· {{Link Toggle 70SselmerriboPsitetRNA}} ·· {{Link Toggle 70SselmerriboEsitetRNA}} ·· <br>
·· {{Link Toggle 70SriboLSU}} ·· {{Link Toggle 70SriboSSU}} ·· {{Link Toggle BlackWhiteBackground}}  ·· <br></center></td></tr></table>

The 70S is so large that the small paromomycin molecule is not readily obvious, and so <scene name='User:Wayne_Decatur/Sandbox_Thermus_70S_With_Paromomycin/70swithparbest/6'>here the view zooms in and paromomycin is highlighted by making the ribosome partially translucent</scene>. 

Returning to  <scene name='User:Wayne_Decatur/Sandbox_Thermus_70S_With_Paromomycin/70swithpar/1'>the initial scene of the full ribosome</scene> now aware of the locale where paromomycinin is bound, it is clear that in the Thermus 70S paromomycin is observed binding to the penultimate helix of the small subunit (helix 44) at the decoding center where the anticodon stem-loop of the <font color = 'pink'>'''A-site tRNA'''</font> contacts the mRNA (shown as yellow).  
<!--After much work, finally got 5S to go transparent by turning off cartoon and making it trace. Others seemed fine with cartoon. See 
<scene name='User:Wayne_Decatur/Sandbox_Thermus_70S_With_Paromomycin/70swithparbest/3'>TextToBeDisplayed</scene>
IN FACT LATER IT SEEMED I HAD TO PASTE SPECIAL LINE IN COMMAND BEFORE SAVING EACH TIME TO GET 5S TO SAVE TRANSPARENT. SPECIAL LINE OF CODE TO PASTE:select 1.1 and :b; cartoon off; trace 1.0; color [x888888];-->

NEED TO DO STILL: Add the e. coli 70S that has two molecules bound

==About these Structure==
[[2j00]] is a 25 chains structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J00 OCA]. 

[[2j01]] is a 31 chains structure of sequences from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J01 OCA].
Versions of [[2j00]] and [[2j01]] optimized for use online as described [[User:Wayne Decatur/Interactions between Antibiotics and the Ribosome|here]] are used on this page. You may wish to examine the ADD LINK basics of the subunit. 

==Reference for the Structures==
<ref group="xtra">PMID:16959973</ref><references group="xtra"/>

==Related Structures==
*[[Large Ribosomal Subunit of Haloarcula|Haloarcula Large Ribosomal Subunit]]
*[[User:Wayne Decatur/Interactions between Antibiotics and the Ribosome|Interactions between Antibiotics and the Ribosome]]


<ref>PMID: 12765838</ref>

==References==
<references />

==Additional Literature and Resources==
<ref group="xtra">PMID:15491801</ref>
<references group="xtra"/> 
*[http://www.youtube.com/watch?v=E6wXlpkQVww Lecture by Venki Ramakrishnan in 2004 entitled The Ribosome: The Cell's Protein-Synthesizing Machine and How Antibiotics Disrupt It] - posted on Brookhaven National Laboratory's Channel
*[http://www.drugbank.ca/drugs/DB01421 Paramomycin at the DrugBank database]
*[http://en.wikipedia.org/wiki/Paromomycin_sulfate Paromomycin sulfate at Wikipedia]
[[Category: Escherichia coli]]
[[Category: Thermus thermophilus]]
[[Category: Dunham, C M.]]
[[Category: Kelley, A C.]]
[[Category: Murphy, F V.]]
[[Category: Petry, S.]]
[[Category: Ramakrishnan, V.]]
[[Category: Selmer, M.]]
[[Category: Weir, J R.]]
[[Category: Weixlbaumer, A.]]
[[Category: Mrna]]
[[Category: Paromomycin]]
[[Category: Ribosome]]
[[Category: Translation]]
[[Category: Trna]]
[[Category: Antibiotic]]
[[Category: 50S]]
[[Category: 30S]]
[[Category: 70S]]
[[Category: Large ribosomal subunit]]
[[Category: Ribosome]]

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