User:Wayne Decatur/Sandbox
From Proteopedia
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<scene name='User:Wayne_Decatur/Sandbox/Test/3'>TextToBeDisplayed</scene> | <scene name='User:Wayne_Decatur/Sandbox/Test/3'>TextToBeDisplayed</scene> | ||
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| + | ==Tamiflu Binds to N1 by Induced Fit== | ||
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| + | <applet load='2hty2hu4_j.pdb' size='500' frame='true' align='right' caption='Morph of N1 alone (2hty) to N1 complexed with Tamiflu (2hu4). The position where Tamiflu will bind is shown translucent except when bound in the empirically-determined model.' scene='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/Morph_2hty_to_2hu4/2' /> | ||
| + | Tamiflu was designed to fit N2/N9, so it is serendipitous that it works on N1. In fact, when the structure of N1 was determined<ref name='Russell2006' />, the <font color='#e07000'><b>loop comprising residues 147-152</b></font> was not in a suitable position to participate in binding Tamiflu. However, the complex of N1 with Tamiflu revealed that this loop is pulled into proper contact with the drug in an [[Induced fit|induced fit]] manner<ref name='Russell2006' />. A [[Morphs|morph]] from N1 alone ([[2hty]]) to N1 complexed with Tamiflu ([[2hu4]])<ref>Chain A from [[2hty]] was morphed to chain A of [[2hu4]] by linear interpolation, inserting 6 intermediate interpolated frames, using the freely available [http://www.umass.edu/microbio/rasmol/pdbtools.htm#martz morph2 program].</ref> shows the change in position of this loop (<scene name='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/Morph_2hty_to_2hu4/8'>replay initial morph</scene>). | ||
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| + | The binding of Tamiflu to N1 pulls the sidechains of two conserved residues, <scene name='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/Morph_2hty_to_2hu4/7'>Asp151, Glu119</scene>, closer to the inhibitor. | ||
Revision as of 11:49, 12 November 2008
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Here is a schematic illustration of the two strands of this silencing RNA (siRNA):
5'-pCGUACGCGUCACGCGUACGUU-OH-3'
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3'-OH-UUGCAUGCGCACUGCGCAUGCp-5'
Tamiflu Binds to N1 by Induced Fit
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Tamiflu was designed to fit N2/N9, so it is serendipitous that it works on N1. In fact, when the structure of N1 was determined[1], the loop comprising residues 147-152 was not in a suitable position to participate in binding Tamiflu. However, the complex of N1 with Tamiflu revealed that this loop is pulled into proper contact with the drug in an induced fit manner[1]. A morph from N1 alone (2hty) to N1 complexed with Tamiflu (2hu4)[2] shows the change in position of this loop ().
The binding of Tamiflu to N1 pulls the sidechains of two conserved residues, , closer to the inhibitor.
