1nnc: Difference between revisions

Revision as of 15:07, 21 February 2008

INFLUENZA VIRUS NEURAMINIDASE SUBTYPE N9 (TERN) COMPLEXED WITH 4-GUANIDINO-NEU5AC2EN INHIBITOR

OverviewOverview

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 StructureAbout this Structure

1NNC is a Single protein structure of sequence from Unidentified influenza 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

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 14:07:55 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1nnc.gif|left|200px]]<br /><applet load="1nnc" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1nnc.gif|left|200px]]<br /><applet load="1nnc" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1nnc, resolution 1.8&Aring;" />
 '''INFLUENZA VIRUS NEURAMINIDASE SUBTYPE N9 (TERN) COMPLEXED WITH 4-GUANIDINO-NEU5AC2EN INHIBITOR'''<br />
 ==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.
+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==
-NNC 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 MAN, NAG, CA and ZMR 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NNC OCA].
+NNC 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=MAN:'>MAN</scene>, <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=ZMR:'>ZMR</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=1NNC OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Unidentified influenza virus]]
-[[Category: Colman, P.M.]]
+[[Category: Colman, P M.]]
-[[Category: Varghese, J.N.]]
+[[Category: Varghese, J N.]]
 [[Category: CA]]
 [[Category: MAN]]
@@ Line 23: / Line 23: @@
 [[Category: sialidase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 22:24:27 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:07:55 2008''