3W09

Influenza virus neuraminidase subtype N9 (TERN) complexed with 2,3-dif guanidino-neu5ac2en inhibitor

3W09 の概要

• エントリーDOI: 10.2210/pdb3w09/pdb
• 関連するPDBエントリー: 1NNC 7NN9
• 分子名称: Neuraminidase, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: neuraminidase, sialidase, hydrolase(o-glucosyl), hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Influenza A virus
• 細胞内の位置: Virion membrane (By similarity): P03472
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46963.80

構造登録者

Streltsov, V.A. (登録日: 2012-10-25, 公開日: 2013-05-01, 最終更新日: 2024-10-16)

主引用文献

Kim, J.-H.,Resende, R.,Wennekes, T.,Chen, H.M.,Bance, N.,Buchini, S.,Watts, A.G.,Pilling, P.,Streltsov, V.A.,Petric, M.,Liggins, R.,Barrett, S.,McKimm-Breschkin, J.L.,Niikura, M.,Withers, S.G.
Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity
Science, 340:71-75, 2013

PubMed Abstract: Influenza antiviral agents play important roles in modulating disease severity and in controlling pandemics while vaccines are prepared, but the development of resistance to agents like the commonly used neuraminidase inhibitor oseltamivir may limit their future utility. We report here on a new class of specific, mechanism-based anti-influenza drugs that function through the formation of a stabilized covalent intermediate in the influenza neuraminidase enzyme, and we confirm this mode of action with structural and mechanistic studies. These compounds function in cell-based assays and in animal models, with efficacies comparable to that of the neuraminidase inhibitor zanamivir and with broad-spectrum activity against drug-resistant strains in vitro. The similarity of their structure to that of the natural substrate and their mechanism-based design make these attractive antiviral candidates.

PubMed: 23429702
DOI: 10.1126/science.1232552

実験手法

X-RAY DIFFRACTION (2 Å)