1ing: Difference between revisions
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==Overview== | ==Overview== | ||
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 .. | 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 Structure== | ==About this Structure== | ||
1ING is a | 1ING 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 CA and ST5 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] Structure known Active Sites: CAA and CAB. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ING OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: sialidase]] | [[Category: sialidase]] | ||
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Revision as of 16:15, 5 November 2007
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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 with CA and ST5 as ligands. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Structure known Active Sites: CAA and CAB. 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
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