1INH

INFLUENZA A SUBTYPE N2 NEURAMINIDASE COMPLEXED WITH AROMATIC BANA111 INHIBITOR

1INH の概要

• エントリーDOI: 10.2210/pdb1inh/pdb
• 分子名称: INFLUENZA A SUBTYPE N2 NEURAMINIDASE, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: neuraminidase, sialidase, hydrolase, o-glycosyl, hydrolase (o-glycosyl)
• 由来する生物種: Influenza A virus
• 細胞内の位置: Virion membrane (By similarity): P06820
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92175.57

構造登録者

Jedrzejas, M.J.,Luo, M. (登録日: 1995-07-07, 公開日: 1996-08-17, 最終更新日: 2024-10-30)

主引用文献

Singh, S.,Jedrzejas, M.J.,Air, G.M.,Luo, M.,Laver, W.G.,Brouillette, W.J.
Structure-based inhibitors of influenza virus sialidase. A benzoic acid lead with novel interaction.
J.Med.Chem., 38:3217-3225, 1995

PubMed Abstract: 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.

PubMed: 7650674
DOI: 10.1021/jm00017a005

実験手法

X-RAY DIFFRACTION (2.4 Å)