7nn9
From Proteopedia
(New page: 200px<br /><applet load="7nn9" size="450" color="white" frame="true" align="right" spinBox="true" caption="7nn9, resolution 2.Å" /> '''NATIVE INFLUENZA VIRUS...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:7nn9.gif|left|200px]]<br /><applet load="7nn9" size=" | + | [[Image:7nn9.gif|left|200px]]<br /><applet load="7nn9" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="7nn9, resolution 2.Å" /> | caption="7nn9, resolution 2.Å" /> | ||
'''NATIVE INFLUENZA VIRUS NEURAMINIDASE SUBTYPE N9 (TERN)'''<br /> | '''NATIVE INFLUENZA VIRUS NEURAMINIDASE SUBTYPE N9 (TERN)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The three-dimensional X-ray structure of a complex of the potent | + | The three-dimensional X-ray structure of a complex of the potent neuraminidase inhibitor 4-guanidino-Neu5Ac2en and influenza virus neuraminidase (Subtype N9) has been obtained utilizing diffraction data to 1.8 A resolution. The interactions of the inhibitor, solvent water molecules, and the active site residues have been accurately determined. Six water molecules bound in the native structure have been displaced by the inhibitor, and the active site residues show no significant conformational changes on binding. Sialic acid, the natural substrate, binds in a half-chair conformation that is isosteric to the inhibitor. The conformation of the inhibitor in the active site of the X-ray structure concurs with that obtained by theoretical calculations and validates the structure-based design of the inhibitor. Comparison of known high-resolution structures of neuraminidase subtypes N2, N9, and B shows good structural conservation of the active site protein atoms, but the location of the water molecules in the respective active sites is less conserved. In particular, the environment of the 4-guanidino group of the inhibitor is strongly conserved and is the basis for the antiviral action of the inhibitor across all presently known influenza strains. Differences in the solvent structure in the active site may be related to variation in the affinities of inhibitors to different subtypes of neuraminidase. |
==About this Structure== | ==About this Structure== | ||
| - | 7NN9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Unidentified_influenza_virus Unidentified influenza virus] with NAG and CA as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 7NN9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Unidentified_influenza_virus Unidentified influenza virus] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 2NN9. 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=7NN9 OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Unidentified influenza virus]] | [[Category: Unidentified influenza virus]] | ||
| - | [[Category: Colman, P | + | [[Category: Colman, P M.]] |
| - | [[Category: Varghese, J | + | [[Category: Varghese, J N.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
| Line 21: | Line 21: | ||
[[Category: sialidase]] | [[Category: sialidase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:17:28 2008'' |
Revision as of 17:17, 21 February 2008
|
NATIVE INFLUENZA VIRUS NEURAMINIDASE SUBTYPE N9 (TERN)
Overview
The three-dimensional X-ray structure of a complex of the potent neuraminidase inhibitor 4-guanidino-Neu5Ac2en and influenza virus neuraminidase (Subtype N9) has been obtained utilizing diffraction data to 1.8 A resolution. The interactions of the inhibitor, solvent water molecules, and the active site residues have been accurately determined. Six water molecules bound in the native structure have been displaced by the inhibitor, and the active site residues show no significant conformational changes on binding. Sialic acid, the natural substrate, binds in a half-chair conformation that is isosteric to the inhibitor. The conformation of the inhibitor in the active site of the X-ray structure concurs with that obtained by theoretical calculations and validates the structure-based design of the inhibitor. Comparison of known high-resolution structures of neuraminidase subtypes N2, N9, and B shows good structural conservation of the active site protein atoms, but the location of the water molecules in the respective active sites is less conserved. In particular, the environment of the 4-guanidino group of the inhibitor is strongly conserved and is the basis for the antiviral action of the inhibitor across all presently known influenza strains. Differences in the solvent structure in the active site may be related to variation in the affinities of inhibitors to different subtypes of neuraminidase.
About this Structure
7NN9 is a Single protein structure of sequence from Unidentified influenza virus with and as ligands. This structure supersedes the now removed PDB entry 2NN9. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Full crystallographic information is available from OCA.
Reference
Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase., Varghese JN, Epa VC, Colman PM, Protein Sci. 1995 Jun;4(6):1081-7. PMID:7549872
Page seeded by OCA on Thu Feb 21 19:17:28 2008
