4WEF

Structure of the Hemagglutinin-neuraminidase from Human parainfluenza virus type III: complex with difluorosialic acid

Summary for 4WEF

• Entry DOI: 10.2210/pdb4wef/pdb
• Related: 1V3C 4WEG
• Descriptor: Hemagglutinin-neuraminidase glycoprotein, beta-D-mannopyranose-(1-3)-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)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• Functional Keywords: neuraminidase, hpiv3 hn, complex, difluorosialic acid, covalent inhibitor, second receptor binding site, viral protein
• Biological source: Human parainfluenza virus 3
• Total number of polymer chains: 2
• Total formula weight: 102825.98

Authors

Streltsov, V.A.,Pilling, P.,Barrett, S.,McKimm-Breschkin, J. (deposition date: 2014-09-10, release date: 2015-09-16, Last modification date: 2023-11-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)