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| <applet load='2hu4_1.pdb' size='500' frame='true' align='right' caption='Influenza Neuraminidase N1 (2hu4).' scene='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/2hu4_tetramer/1' />
| | ==Chemistry of Water and Its Hydrogen Bonds== |
| | Prepared in collaboration with [[User:Gabriel Pons]]. |
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| ===Neuraminidase Structure and Conserved Amino Acids=== | | ===One Molecule=== |
| | <applet size='400' frame='true' align='right' caption='Insert caption here' |
| | scene='User:Eric_Martz/Sandbox_8/Water/2' /> |
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| *Influenza neuraminidase is a homotetramer<ref>The tetramer is one of two [[Biological Unit|biological units]] in the [[Asymmetric Unit|asymmetric unit]] of [[2hu4]].</ref> (<scene name='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/2hu4_tetramer/1'>restore initial scene</scene>). | | *(<scene name='User:Eric_Martz/Sandbox_8/Water/2'>restore initial scene</scene>) |
| | *<scene name='User:Eric_Martz/Sandbox_8/Water/4'>partial charge values</scene> |
| | *<scene name='User:Eric_Martz/Sandbox_8/Water/6'>shape of the molecule (spacefilling)</scene> (van der Waals radii) |
| | *<scene name='User:Eric_Martz/Sandbox_8/Water/5'>translucent surface colored by molecular electrostatic potential</scene> <font color="blue"><b>Positive (+)</b></font>, <font color="red"><b>Negative (-)</b></font> |
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| *Each of the four protein chains in the tetramer has a catalytic site, indicated in <scene name='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/2hu4_tetramer/10'>this scene</scene> by the positions of the bound <font color='red'>'''Tamiflu'''</font> inhibitors.
| | ---- |
| | ===Technical Information=== |
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| *The <scene name='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/2hu4_monomer/2'>substrate binding site</scene> involves only a single protein chain, being distant from neighboring chains. | | The following scene demonstrates a problem with greek letters in labels in Jmol |
| | *<scene name='User:Eric_Martz/Sandbox_8/Water/3'>partial charges</scene> (using δ in the label, it gets corrupted) |
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| *The <scene name='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/2hu4_monomer_sec_struct/1'>secondary structure</scene> is mostly beta, consisting of several beta sheets with three short alpha helices ({{Template:ColorKey_Strand}}, {{Template:ColorKey_Helix}}).
| | Script for translucent MEP colored surface: |
| | <pre> |
| | {hydrogen}.partialCharge = 0.41 |
| | {oxygen}.partialCharge = -0.82 |
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| *The residues contacting the <font color='red'>'''Tamiflu inhibitory substrate analog'''</font> are <scene name='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/2hu4_monomer_consurf/1'>highly conserved</scene><ref>See [[Evolutionary Conservation]]. Coloring by ConSurf on chain A of 2hu4 based on 100 unique homologs using default conditions, done on September 23, 2008.</ref>.
| | # IMPORTANT: the SOLVENT version of isosurface |
| <center>{{Template:ColorKey_ConSurf}}</center>
| | # IGNORES WATER UNCONDITIONALLY! We must us MOLECULAR! |
| | #isosurface resolution 6 MOLECULAR colorscheme "rwb" map MEP |
| | isosurface resolution 6 MOLECULAR map MEP |
| | # Higher values of resolution make a choppier surface that rotates |
| | # more jerkily. 6 is good. |
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| *These highly conserved residues include some known to be crucial to binding sialic acid substrate: Arg 118, Arg 292 and Arg 371 bind the carboxylate; Arg 152 interacts with the acetamido substituent; and Glu 276 forms hydrogen bonds with the 8- and 9-hydroxyl groups of the substrate. These residues are <scene name='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/2hu4_monomer_activesite/1'>highlighted here</scene> in contact with the sialic acid substrate analog Tamiflu. In this scene, atoms and bonds in Tamiflu and the highlighted residues are colored by element: {{Template:ColorKey_Element_C}}, {{Template:ColorKey_Element_O}}, {{Template:ColorKey_Element_N}}.
| | color isosurface "rwb" range -0.2 0.2 |
| | # chose this range by trial and error. |
| | # default is -0.1 0.1 as reported by the isosurface command. |
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| | color isosurface translucent 2 |
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| | # or the partial charges could be in the PDB file using |
| | # this command to transfer the values. |
| | # {*}.partialCharge = {*}.temperature.all |
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| | </pre> |
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| | Possible script for large translucent hbonds: |
| | <pre> |
| | select all |
| | calculate hbonds |
| | hbonds 0.3 |
| | color hbonds white |
| | color hbonds translucent 6 |
| | </pre> |