4WEG

influenza virus neuraminidase N9 in complex 2,3-difluorosialic acid

4WEG の概要

• エントリーDOI: 10.2210/pdb4weg/pdb
• 関連するPDBエントリー: 1NNC 4WEF
• 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)]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, ... (9 entities in total)
• 機能のキーワード: influenza virus neuraminidase, n9, complex, 2, 3-difluorosialic acid, second binding site, hydrolase
• 由来する生物種: Influenza A virus (A/tern/Australia/G70C/1975(H11N9))
• 細胞内の位置: Virion membrane : P03472
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46772.46

構造登録者

Streltsov, V.A.,Pilling, P.,Barrett, S.,McKimm-Breschkin, J. (登録日: 2014-09-10, 公開日: 2015-09-16, 最終更新日: 2024-11-13)

主引用文献

Streltsov, V.A.,Pilling, P.,Barrett, S.,McKimm-Breschkin, J.L.
Catalytic mechanism and novel receptor binding sites of human parainfluenza virus type 3 hemagglutinin-neuraminidase (hPIV3 HN)
Antiviral Res., 123:216-223, 2015

PubMed Abstract: The human parainfluenza virus type 3 (hPIV3) hemagglutinin-neuraminidase (HN) has opposing functions of binding sialic acid receptors and cleaving them, facilitating virus release. The crystal structure of hPIV3 HN complexed with the substrate analogue difluorosialic acid (DFSA) revealed that catalysis by HN involves the formation of a covalently linked sialosyl-enzyme intermediate which was trapped along with a transition-state analogue resembling an oxocarbenium ion. This mechanism of enzyme catalysis was also confirmed in the crystal structure of the influenza N9 neuraminidase complexed with DFSA. Additionally, novel secondary receptor binding sites were identified in the hPIV3 HN-DFSA complex including one near the catalytic cavity which upon binding DFSA imposes subtle changes and may help the HN balance the opposing functions. Multiple receptor binding sites may increase avidity to facilitate cell binding and fusion promotion. The secondary receptor binding sites in the paramyxoviruses are so far unique to each virus type.

PubMed: 26364554
DOI: 10.1016/j.antiviral.2015.08.014

実験手法

X-RAY DIFFRACTION (2.1 Å)