PDBsum entry 1usx

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Hydrolase PDB id
Jmol PyMol
Protein chains
447 a.a. *
DAN ×3
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of the newcastle disease virus hemagglutinin-neuraminidase complexed with thiosialoside
Structure: Hemagglutinin-neuraminidase glycoprotein. Chain: a, b, c. Fragment: head domain, residues 124-577. Ec:
Source: Newcastle disease virus. Organism_taxid: 11176. Strain: kansas
Biol. unit: Tetramer (from PDB file)
2.70Å     R-factor:   0.225     R-free:   0.289
Authors: V.Zaitsev,M.Von Itzstein,D.Groves,M.Kiefel,T.Takimoto, A.Portner,G.Taylor
Key ref: V.Zaitsev et al. (2004). Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: implications for fusion. J Virol, 78, 3733-3741. PubMed id: 15016893
01-Dec-03     Release date:   19-Mar-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P32884  (HN_NDVB) -  Hemagglutinin-neuraminidase
577 a.a.
447 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Exo-alpha-sialidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)-glycosidic linkages of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     viral envelope   1 term 
  Biological process     viral infectious cycle   1 term 
  Biochemical function     host cell surface receptor binding     1 term  


J Virol 78:3733-3741 (2004)
PubMed id: 15016893  
Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: implications for fusion.
V.Zaitsev, M.von Itzstein, D.Groves, M.Kiefel, T.Takimoto, A.Portner, G.Taylor.
Paramyxoviruses are the leading cause of respiratory disease in children. Several paramyxoviruses possess a surface glycoprotein, the hemagglutinin-neuraminidase (HN), that is involved in attachment to sialic acid receptors, promotion of fusion, and removal of sialic acid from infected cells and progeny virions. Previously we showed that Newcastle disease virus (NDV) HN contained a pliable sialic acid recognition site that could take two states, a binding state and a catalytic state. Here we present evidence for a second sialic acid binding site at the dimer interface of HN and present a model for its involvement in cell fusion. Three different crystal forms of NDV HN now reveal identical tetrameric arrangements of HN monomers, perhaps indicative of the tetramer association found on the viral surface.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21123551 C.Estevez, D.J.King, M.Luo, and Q.Yu (2011).
A single amino acid substitution in the haemagglutinin-neuraminidase protein of Newcastle disease virus results in increased fusion promotion and decreased neuraminidase activities without changes in virus pathotype.
  J Gen Virol, 92, 544-551.  
  21438845 S.Ge, and Z.Wang (2011).
An overview of influenza A virus receptors.
  Crit Rev Microbiol, 37, 157-165.  
21217702 T.Hashiguchi, T.Ose, M.Kubota, N.Maita, J.Kamishikiryo, K.Maenaka, and Y.Yanagi (2011).
Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM.
  Nat Struct Mol Biol, 18, 135-141.
PDB codes: 3alw 3alx 3alz
21085573 O.F.Maminiaina, P.Gil, F.X.Briand, E.Albina, D.Keita, H.R.Andriamanivo, V.Chevalier, R.Lancelot, D.Martinez, R.Rakotondravao, J.J.Rajaonarison, M.Koko, A.A.Andriantsimahavandy, V.Jestin, and R.Servan de Almeida (2010).
Newcastle disease virus in Madagascar: identification of an original genotype possibly deriving from a died out ancestor of genotype IV.
  PLoS One, 5, e13987.  
20375167 T.A.Bowden, M.Crispin, D.J.Harvey, E.Y.Jones, and D.I.Stuart (2010).
Dimeric architecture of the Hendra virus attachment glycoprotein: evidence for a conserved mode of assembly.
  J Virol, 84, 6208-6217.
PDB code: 2x9m
20053750 V.P.Mishin, M.Watanabe, G.Taylor, J.Devincenzo, M.Bose, A.Portner, and I.V.Alymova (2010).
N-linked glycan at residue 523 of human parainfluenza virus type 3 hemagglutinin-neuraminidase masks a second receptor-binding site.
  J Virol, 84, 3094-3100.  
20661635 Z.Ding, Y.L.Cong, S.Chang, G.M.Wang, Z.Wang, Q.P.Zhang, H.Wu, and Y.Z.Sun (2010).
Genetic analysis of avian paramyxovirus-1 (Newcastle disease virus) isolates obtained from swine populations in China related to commonly utilized commercial vaccine strains.
  Virus Genes, 41, 369-376.  
20204429 Z.J.Li, Y.Li, S.Chang, Z.Ding, L.Z.Mu, and Y.L.Cong (2010).
Antigenic variation between Newcastle disease viruses of goose and chicken origin.
  Arch Virol, 155, 499-505.  
19052089 A.Krishnan, S.K.Verma, P.Mani, R.Gupta, S.Kundu, and D.P.Sarkar (2009).
A histidine switch in hemagglutinin-neuraminidase triggers paramyxovirus-cell membrane fusion.
  J Virol, 83, 1727-1741.  
19031463 D.Shah, S.Vidal, M.A.Link, S.A.Rubin, and K.E.Wright (2009).
Identification of genetic mutations associated with attenuation and changes in tropism of Urabe mumps virus.
  J Med Virol, 81, 130-138.  
19878307 E.C.Smith, A.Popa, A.Chang, C.Masante, and R.E.Dutch (2009).
Viral entry mechanisms: the increasing diversity of paramyxovirus entry.
  FEBS J, 276, 7217-7227.  
19019819 H.C.Aguilar, Z.A.Ataman, V.Aspericueta, A.Q.Fang, M.Stroud, O.A.Negrete, R.A.Kammerer, and B.Lee (2009).
A novel receptor-induced activation site in the Nipah virus attachment glycoprotein (G) involved in triggering the fusion glycoprotein (F).
  J Biol Chem, 284, 1628-1635.  
19458903 J.Uhlendorff, T.Matrosovich, H.D.Klenk, and M.Matrosovich (2009).
Functional significance of the hemadsorption activity of influenza virus neuraminidase and its alteration in pandemic viruses.
  Arch Virol, 154, 945-957.  
19515783 M.Jarahian, C.Watzl, P.Fournier, A.Arnold, D.Djandji, S.Zahedi, A.Cerwenka, A.Paschen, V.Schirrmacher, and F.Momburg (2009).
Activation of natural killer cells by newcastle disease virus hemagglutinin-neuraminidase.
  J Virol, 83, 8108-8121.  
  20161127 R.M.Iorio, V.R.Melanson, and P.J.Mahon (2009).
Glycoprotein interactions in paramyxovirus fusion.
  Future Virol, 4, 335-351.  
19342221 T.Stehle, and J.M.Casasnovas (2009).
Specificity switching in virus-receptor complexes.
  Curr Opin Struct Biol, 19, 181-188.  
18579600 I.V.Alymova, G.Taylor, V.P.Mishin, M.Watanabe, K.G.Murti, K.Boyd, P.Chand, Y.S.Babu, and A.Portner (2008).
Loss of the N-linked glycan at residue 173 of human parainfluenza virus type 1 hemagglutinin-neuraminidase exposes a second receptor-binding site.
  J Virol, 82, 8400-8410.  
18568847 J.M.White, S.E.Delos, M.Brecher, and K.Schornberg (2008).
Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme.
  Crit Rev Biochem Mol Biol, 43, 189-219.  
18799571 K.A.Bishop, A.C.Hickey, D.Khetawat, J.R.Patch, K.N.Bossart, Z.Zhu, L.F.Wang, D.S.Dimitrov, and C.C.Broder (2008).
Residues in the stalk domain of the hendra virus g glycoprotein modulate conformational changes associated with receptor binding.
  J Virol, 82, 11398-11409.  
18521536 M.Xu, S.Chang, Z.Ding, H.W.Gao, J.Y.Wan, W.S.Liu, L.N.Liu, Y.Gao, and J.Xu (2008).
Genomic analysis of Newcastle disease virus strain NA-1 isolated from geese in China.
  Arch Virol, 153, 1281-1289.  
18753211 P.J.Mahon, A.M.Mirza, T.A.Musich, and R.M.Iorio (2008).
Engineered intermonomeric disulfide bonds in the globular domain of Newcastle disease virus hemagglutinin-neuraminidase protein: implications for the mechanism of fusion promotion.
  J Virol, 82, 10386-10396.  
18597807 P.Yuan, G.P.Leser, B.Demeler, R.A.Lamb, and T.S.Jardetzky (2008).
Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein.
  Virology, 378, 282-291.  
18346895 R.M.Iorio, and P.J.Mahon (2008).
Paramyxoviruses: different receptors - different mechanisms of fusion.
  Trends Microbiol, 16, 135-137.  
19122383 T.Hashiguchi, K.Maenaka, and Y.Yanagi (2008).
X-ray crystallographic analysis of measles virus hemagglutinin.
  Uirusu, 58, 1.  
17301148 H.C.Aguilar, K.A.Matreyek, D.Y.Choi, C.M.Filone, S.Young, and B.Lee (2007).
Polybasic KKR motif in the cytoplasmic tail of Nipah virus fusion protein modulates membrane fusion by inside-out signaling.
  J Virol, 81, 4520-4532.  
17567695 L.M.Palermo, M.Porotto, O.Greengard, and A.Moscona (2007).
Fusion promotion by a paramyxovirus hemagglutinin-neuraminidase protein: pH modulation of receptor avidity of binding sites I and II.
  J Virol, 81, 9152-9161.  
17229690 M.Porotto, M.Fornabaio, G.E.Kellogg, and A.Moscona (2007).
A second receptor binding site on human parainfluenza virus type 3 hemagglutinin-neuraminidase contributes to activation of the fusion mechanism.
  J Virol, 81, 3216-3228.  
18003910 T.Hashiguchi, M.Kajikawa, N.Maita, M.Takeda, K.Kuroki, K.Sasaki, D.Kohda, Y.Yanagi, and K.Maenaka (2007).
Crystal structure of measles virus hemagglutinin provides insight into effective vaccines.
  Proc Natl Acad Sci U S A, 104, 19535-19540.
PDB codes: 2zb5 2zb6
16863077 A.Römer-Oberdörfer, J.Veits, O.Werner, and T.C.Mettenleiter (2006).
Enhancement of pathogenicity of Newcastle disease virus by alteration of specific amino acid residues in the surface glycoproteins F and HN.
  Avian Dis, 50, 259-263.  
16678421 C.J.Russell, and L.E.Luque (2006).
The structural basis of paramyxovirus invasion.
  Trends Microbiol, 14, 243-246.  
16575531 C.Ryan, V.Zaitsev, D.J.Tindal, J.C.Dyason, R.J.Thomson, I.Alymova, A.Portner, M.von Itzstein, and G.Taylor (2006).
Structural analysis of a designed inhibitor complexed with the hemagglutinin-neuraminidase of Newcastle disease virus.
  Glycoconj J, 23, 135-141.  
16575518 E.Villar, and I.M.Barroso (2006).
Role of sialic acid-containing molecules in paramyxovirus entry into the host cell: a minireview.
  Glycoconj J, 23, 5.  
16641279 H.C.Aguilar, K.A.Matreyek, C.M.Filone, S.T.Hashimi, E.L.Levroney, O.A.Negrete, A.Bertolotti-Ciarlet, D.Y.Choi, I.McHardy, J.A.Fulcher, S.V.Su, M.C.Wolf, L.Kohatsu, L.G.Baum, and B.Lee (2006).
N-glycans on Nipah virus fusion protein protect against neutralization but reduce membrane fusion and viral entry.
  J Virol, 80, 4878-4889.  
16501098 L.W.McGinnes, and T.G.Morrison (2006).
Inhibition of receptor binding stabilizes Newcastle disease virus HN and F protein-containing complexes.
  J Virol, 80, 2894-2903.  
16414997 M.Porotto, M.Fornabaio, O.Greengard, M.T.Murrell, G.E.Kellogg, and A.Moscona (2006).
Paramyxovirus receptor-binding molecules: engagement of one site on the hemagglutinin-neuraminidase protein modulates activity at the second site.
  J Virol, 80, 1204-1213.  
17093041 S.A.Connolly, G.P.Leser, H.S.Yin, T.S.Jardetzky, and R.A.Lamb (2006).
Refolding of a paramyxovirus F protein from prefusion to postfusion conformations observed by liposome binding and electron microscopy.
  Proc Natl Acad Sci U S A, 103, 17903-17908.  
16940513 T.Bousse, and T.Takimoto (2006).
Mutation at residue 523 creates a second receptor binding site on human parainfluenza virus type 1 hemagglutinin-neuraminidase protein.
  J Virol, 80, 9009-9016.  
16378965 V.R.Melanson, and R.M.Iorio (2006).
Addition of N-glycans in the stalk of the Newcastle disease virus HN protein blocks its interaction with the F protein and prevents fusion.
  J Virol, 80, 623-633.  
16007245 A.Moscona (2005).
Entry of parainfluenza virus into cells as a target for interrupting childhood respiratory disease.
  J Clin Invest, 115, 1688-1698.  
16557006 M.Tsurudome (2005).
[Viral fusion mechanisms]
  Uirusu, 55, 207-219.  
15893670 P.Yuan, T.B.Thompson, B.A.Wurzburg, R.G.Paterson, R.A.Lamb, and T.S.Jardetzky (2005).
Structural studies of the parainfluenza virus 5 hemagglutinin-neuraminidase tetramer in complex with its receptor, sialyllactose.
  Structure, 13, 803-815.
PDB codes: 1z4v 1z4w 1z4x 1z4y 1z4z 1z50
15564499 M.Porotto, M.Murrell, O.Greengard, M.C.Lawrence, J.L.McKimm-Breschkin, and A.Moscona (2004).
Inhibition of parainfluenza virus type 3 and Newcastle disease virus hemagglutinin-neuraminidase receptor binding: effect of receptor avidity and steric hindrance at the inhibitor binding sites.
  J Virol, 78, 13911-13919.  
15542686 T.L.Bousse, G.Taylor, S.Krishnamurthy, A.Portner, S.K.Samal, and T.Takimoto (2004).
Biological significance of the second receptor binding site of Newcastle disease virus hemagglutinin-neuraminidase protein.
  J Virol, 78, 13351-13355.  
15542657 V.R.Melanson, and R.M.Iorio (2004).
Amino acid substitutions in the F-specific domain in the stalk of the newcastle disease virus HN protein modulate fusion and interfere with its interaction with the F protein.
  J Virol, 78, 13053-13061.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.