1f8b: Difference between revisions

Revision as of 13:36, 21 February 2008

NATIVE INFLUENZA VIRUS NEURAMINIDASE IN COMPLEX WITH NEU5AC2EN

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

1F8B 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

Page seeded by OCA on Thu Feb 21 12:36:09 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:1f8b.gif|left|200px]]<br /><applet load="1f8b" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1f8b.gif|left|200px]]<br /><applet load="1f8b" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1f8b, resolution 1.8&Aring;" />
 '''NATIVE INFLUENZA VIRUS NEURAMINIDASE IN COMPLEX WITH NEU5AC2EN'''<br />
 ==Overview==
-,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.
+,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==
-F8B 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 DAN 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=1F8B OCA].
+F8B 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=DAN:'>DAN</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=1F8B OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Influenza a virus]]
 [[Category: Single protein]]
-[[Category: Colman, P.M.]]
+[[Category: Colman, P M.]]
 [[Category: Danylec, B.]]
-[[Category: Itzstein, M.Von.]]
+[[Category: Itzstein, M Von.]]
-[[Category: Smith, B.J.]]
+[[Category: Smith, B J.]]
-[[Category: Varghese, J.N.]]
+[[Category: Varghese, J N.]]
 [[Category: CA]]
 [[Category: DAN]]
@@ Line 28: / Line 28: @@
 [[Category: neuraminidase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 14:42:07 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:36:09 2008''