1ing: Difference between revisions

Revision as of 20:11, 2 May 2008

INFLUENZA A SUBTYPE N2 NEURAMINIDASE COMPLEXED WITH AROMATIC BANA109 INHIBITOR

OverviewOverview

Influenza virus sialidase is a surface enzyme that is essential for infection of the virus. The catalytic site is highly conserved among all known influenza variants, suggesting that this protein is a suitable target for drug intervention. The most potent known inhibitors are analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en), particularly the 4-guanidino derivative (4-guanidino-Neu5Ac2en). We utilized the benzene ring of 4-(N-acetylamino)benzoic acids as a cyclic template to substitute for the dihydropyran ring of Neu5Ac2en. In this study several 3-(N-acylamino) derivatives were prepared as potential replacements for the glycerol side chain of Neu5Ac2en, and some were found to interact with the same binding subsite of sialidase. Of greater significance was the observation that the 3-guanidinobenzoic acid derivative (equivalent to the 4-guanidino grouping of 4-guanidino-Neu5Ac2en), the most potent benzoic acid inhibitor of influenza sialidase thus far identified (IC50 = 10 microM), occupied the glycerol-binding subsite on sialidase as opposed to the guanidino-binding subsite. This benzoic acid derivative thus provides a new compound that interacts in a novel manner with the catalytic site of influenza sialidase.

About this StructureAbout this Structure

1ING is a Single protein structure of sequence from Influenza a virus subtype n2. Full crystallographic information is available from OCA.

ReferenceReference

Structure-based inhibitors of influenza virus sialidase. A benzoic acid lead with novel interaction., Singh S, Jedrzejas MJ, Air GM, Luo M, Laver WG, Brouillette WJ, J Med Chem. 1995 Aug 18;38(17):3217-25. PMID:7650674 Page seeded by OCA on Fri May 2 20:11:18 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:1ing.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1ing |SIZE=350|CAPTION= <scene name='initialview01'>1ing</scene>, resolution 2.4&Aring;
+The line below this paragraph, containing "STRUCTURE_1ing", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=CAA:Substrate+(Sialic+Acid)+Binding+Residues+Catalytic+Site+...'>CAA</scene> and <scene name='pdbsite=CAB:Substrate+(Sialic+Acid)+Binding+Residues+Catalytic+Site+...'>CAB</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ST5:4-(ACETYLAMINO)-3-[(HYDROXYACETYL)AMINO]BENZOIC+ACID'>ST5</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1ing|  PDB=1ing  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ing FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ing OCA], [http://www.ebi.ac.uk/pdbsum/1ing PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ing RCSB]</span>
-}}
 '''INFLUENZA A SUBTYPE N2 NEURAMINIDASE COMPLEXED WITH AROMATIC BANA109 INHIBITOR'''
@@ Line 28: / Line 25: @@
 [[Category: Jedrzejas, M J.]]
 [[Category: Luo, M.]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: neuraminidase]]
+[[Category: Neuraminidase]]
-[[Category: o-glycosyl]]
+[[Category: O-glycosyl]]
-[[Category: sialidase]]
+[[Category: Sialidase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 20:11:18 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:22:09 2008''