Exposing the flexibility of human parainfluenza virus hemagglutinin-neuraminidase.
Human parainfluenza virus type 3 (hPIV-3) is a clinically significant pathogen and is the causative agent of pneumonia and bronchiolitis in children. In this study the solution dynamics of human parainfluenza type 3 hemagglutinin-neuraminidase (HN) have been investigated. A flexible loop around Asp216 that adopts an open conformation in direct vicinity of the active site of the apo-form of the protein and closes upon inhibitor binding has been identified. To date, no available X-ray crystal structure has shown the molecular dynamics simulation-derived predominant loop-conformation states found in the present study. The outcomes of this study provide additional insight into the dynamical properties of hPIV-3 HN and may have important implications in defining HN glycan recognition events, receptor specificity, and antiparainfluenza virus drug discovery.
Institute for Glycomics, Gold Coast Campus, Griffith University Queensland, 4222, Australia. m.winger@griffith.edu.au
Moritz
M
Winger
Mark
M
von Itzstein
D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015707:HN Protein / Q000737:chemistry*; D006801:Humans; D056004:Molecular Dynamics Simulation; D010224:Parainfluenza Virus 3, Human / Q000737:chemistry* / Q000201:enzymology*; D011487:Protein Conformation; D010253:Respirovirus Infections / Q000821:virology
D015707:HN Protein