1inh: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1inh.gif|left|200px]]<br /><applet load="1inh" size=" | [[Image:1inh.gif|left|200px]]<br /><applet load="1inh" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1inh, resolution 2.4Å" /> | caption="1inh, resolution 2.4Å" /> | ||
'''INFLUENZA A SUBTYPE N2 NEURAMINIDASE COMPLEXED WITH AROMATIC BANA111 INHIBITOR'''<br /> | '''INFLUENZA A SUBTYPE N2 NEURAMINIDASE COMPLEXED WITH AROMATIC BANA111 INHIBITOR'''<br /> | ||
| Line 7: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
1INH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_subtype_n2 Influenza a virus subtype n2] with NAG, CA and ST6 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] Known structural/functional Sites: <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>. Full crystallographic information is available from [http:// | 1INH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_subtype_n2 Influenza a virus subtype n2] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=ST6:'>ST6</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] Known structural/functional Sites: <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>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1INH OCA]. | ||
==Reference== | ==Reference== | ||
| Line 24: | Line 24: | ||
[[Category: sialidase]] | [[Category: sialidase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:50:39 2008'' | ||
Revision as of 10:50, 3 February 2008
|
INFLUENZA A SUBTYPE N2 NEURAMINIDASE COMPLEXED WITH AROMATIC BANA111 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
1INH is a Single protein structure of sequence from Influenza a virus subtype n2 with , and as ligands. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Known structural/functional Sites: and . 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 Sun Feb 3 09:50:39 2008