1f8d: Difference between revisions
New page: left|200px<br /><applet load="1f8d" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f8d, resolution 1.40Å" /> '''NATIVE INFLUENZA NEU... |
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[[Image:1f8d.gif|left|200px]]<br /><applet load="1f8d" size=" | [[Image:1f8d.gif|left|200px]]<br /><applet load="1f8d" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1f8d, resolution 1.40Å" /> | caption="1f8d, resolution 1.40Å" /> | ||
'''NATIVE INFLUENZA NEURAMINIDASE IN COMPLEX WITH 9-AMINO-2-DEOXY-2,3-DEHYDRO-N-NEURAMINIC ACID'''<br /> | '''NATIVE INFLUENZA NEURAMINIDASE IN COMPLEX WITH 9-AMINO-2-DEOXY-2,3-DEHYDRO-N-NEURAMINIC ACID'''<br /> | ||
==Overview== | ==Overview== | ||
2,3-didehydro-2-deoxy-N:-acetylneuraminic acid (DANA) is a transition | 2,3-didehydro-2-deoxy-N:-acetylneuraminic acid (DANA) is a transition state analog inhibitor of influenza virus neuraminidase (NA). Replacement of the hydroxyl at the C9 position in DANA and 4-amino-DANA with an amine group, with the intention of taking advantage of an increased electrostatic interaction with a conserved acidic group in the active site to improve inhibitor binding, significantly reduces the inhibitor activity of both compounds. The three-dimensional X-ray structure of the complexes of these ligands and NA was obtained to 1.4 A resolution and showed that both ligands bind isosterically to DANA. Analysis of the geometry of the ammonium at the C4 position indicates that Glu119 may be neutral when these ligands bind. A computational analysis of the binding energies indicates that the substitution is successful in increasing the energy of interaction; however, the gains that are made are not sufficient to overcome the energy that is required to desolvate that part of the ligand that comes in contact with the protein. | ||
==About this Structure== | ==About this Structure== | ||
1F8D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus] with NAG, CA and 9AM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] Full crystallographic information is available from [http:// | 1F8D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=9AM:'>9AM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F8D OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Influenza a virus]] | [[Category: Influenza a virus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Colman, P | [[Category: Colman, P M.]] | ||
[[Category: Danylec, B.]] | [[Category: Danylec, B.]] | ||
[[Category: Itzstein, M | [[Category: Itzstein, M Von.]] | ||
[[Category: Smith, B | [[Category: Smith, B J.]] | ||
[[Category: Varghese, J | [[Category: Varghese, J N.]] | ||
[[Category: 9AM]] | [[Category: 9AM]] | ||
[[Category: CA]] | [[Category: CA]] | ||
| Line 28: | Line 28: | ||
[[Category: neuraminidase]] | [[Category: neuraminidase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:35:57 2008'' | ||
Revision as of 13:35, 21 February 2008
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NATIVE INFLUENZA NEURAMINIDASE IN COMPLEX WITH 9-AMINO-2-DEOXY-2,3-DEHYDRO-N-NEURAMINIC ACID
OverviewOverview
2,3-didehydro-2-deoxy-N:-acetylneuraminic acid (DANA) is a transition state analog inhibitor of influenza virus neuraminidase (NA). Replacement of the hydroxyl at the C9 position in DANA and 4-amino-DANA with an amine group, with the intention of taking advantage of an increased electrostatic interaction with a conserved acidic group in the active site to improve inhibitor binding, significantly reduces the inhibitor activity of both compounds. The three-dimensional X-ray structure of the complexes of these ligands and NA was obtained to 1.4 A resolution and showed that both ligands bind isosterically to DANA. Analysis of the geometry of the ammonium at the C4 position indicates that Glu119 may be neutral when these ligands bind. A computational analysis of the binding energies indicates that the substitution is successful in increasing the energy of interaction; however, the gains that are made are not sufficient to overcome the energy that is required to desolvate that part of the ligand that comes in contact with the protein.
About this StructureAbout this Structure
1F8D is a Single protein structure of sequence from Influenza a virus with , and as ligands. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Full crystallographic information is available from OCA.
ReferenceReference
Analysis of inhibitor binding in influenza virus neuraminidase., Smith BJ, Colman PM, Von Itzstein M, Danylec B, Varghese JN, Protein Sci. 2001 Apr;10(4):689-96. PMID:11274459
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