User:Eric Martz/Sandbox 6: Difference between revisions

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<applet size='450' frame='true' align='right' caption='Insert caption here'
<applet size='450' frame='true' align='right' caption='Insert caption here'
scene='User:Eric_Martz/Sandbox_6/2hu4_3cl0_aligned/2' />
scene='User:Eric_Martz/Sandbox_6/2hu4_3cl0_aligned/4' />


H274Y ([[Amino Acids#Histidine|Histidine]] to [[Amino Acids#Tyrosine|Tyrosine]]) common mutation in the neuraminidase N1 of Influenza A (e.g. H1N1, H5N1).
H274Y ([[Amino Acids#Histidine|Histidine]] to [[Amino Acids#Tyrosine|Tyrosine]]) is the most common mutation conferring resistance to the drug Tamiflu in the neuraminidase N1 of Influenza A (e.g. H1N1, H5N1). Although resistant, this mutant N1 still binds Tamiflu weakly, and a crystal structure was obtained, [[3ckz]]. Below, this is compared to the wild type, [[2hu4]]], using structural alignment of a single protein chain:Tamiflu complex from each.


Tamiflu is shown as thick sticks. Atoms contacting Tamiflu are shown as balls. Amino acids that contain contacting atoms, plus amino acid 274, are shown as thin sticks. All other amino acids are hidden.
'''Why is the affinity of Tamiflu reduced by the mutation H274Y?''' Use the scenes below to help answer this question.
 
Tamiflu is shown as thick sticks. Atoms contacting Tamiflu (4 &Aring;) are shown as balls. Amino acids that contain contacting atoms, plus amino acid 274, are shown as thin sticks. All other amino acids are hidden.


Influenza neuraminidase N1:
Influenza neuraminidase N1:
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<jmol>
<jmol>
<jmolButton>
<jmolButton>
<script>frame 1.1</script>
<script>anim off; frame 1.2</script>
<text>Wild Type</text>
<text>H274Y</text>
</jmolButton>
</jmolButton>
</jmol>
</jmol>
<jmol>
<jmol>
<jmolButton>
<jmolButton>
<script>frame 1.2</script>
<script>anim off; frame 1.1</script>
<text>H274Y</text>
<text>Wild Type</text>
</jmolButton>
</jmolButton>
</jmol>
</jmol>
<jmol>
<jmol>
<jmolButton>
<jmolButton>
<script>frame 0</script>
<script>anim off; frame 0</script>
<text>Both</text>
<text>Both</text>
</jmolButton>
</jmolButton>
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<jmol>
<jmol>
<jmolButton>
<jmolButton>
<script>if (~animation); if (_animating); anim pause;set echo bottom left; color echo white; font echo 20 sansserif;echo Animation Paused; else; anim mode loop 0 0;anim fps 2; anim resume; set echo off;endif;endif;</script>
<script>if (~animation); if (_animating); anim pause; else; anim mode loop 0 0;anim fps 2; anim resume; endif; endif;</script>
<text>Toggle Animation</text>
<text>Toggle Animation</text>
</jmolButton>
</jmolButton>
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Atoms are colored by element:
Atoms are colored by element:
{{Template:ColorKey_Element_C}}
{{Template:ColorKey_Element_C}},
{{Template:ColorKey_Element_N}},
{{Template:ColorKey_Element_O}} (in protein),
<font color="magenta"><b>O</b></font> (in water).

Latest revision as of 06:41, 24 May 2009

Insert caption here

Drag the structure with the mouse to rotate

H274Y (Histidine to Tyrosine) is the most common mutation conferring resistance to the drug Tamiflu in the neuraminidase N1 of Influenza A (e.g. H1N1, H5N1). Although resistant, this mutant N1 still binds Tamiflu weakly, and a crystal structure was obtained, 3ckz. Below, this is compared to the wild type, 2hu4], using structural alignment of a single protein chain:Tamiflu complex from each.

Why is the affinity of Tamiflu reduced by the mutation H274Y? Use the scenes below to help answer this question.

Tamiflu is shown as thick sticks. Atoms contacting Tamiflu (4 Å) are shown as balls. Amino acids that contain contacting atoms, plus amino acid 274, are shown as thin sticks. All other amino acids are hidden.

Influenza neuraminidase N1:

Atoms are colored by element: C, N, O (in protein), O (in water).