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Hydrolase PDB id
1mwe
Jmol
Contents
Protein chain
388 a.a. *
Ligands
NAG-NAG-BMA-MAN-
MAN-MAN-MAN-MAN-
MAN
NAG ×3
SIA ×2
Metals
_CA ×2
Waters ×396
* Residue conservation analysis
PDB id:
1mwe
Name: Hydrolase
Title: The x-ray structure of a complex of tern n9 influenza virus neuraminidase complexed with sialic acid at 4 degrees c rev second sialic acid binding site
Structure: Neuraminidase. Chain: a. Fragment: residues 82 - 468. Synonym: sialidase. Ec: 3.2.1.18
Source: Influenza a virus. Organism_taxid: 11320. Strain: a/tern/australia/g70c/75. Other_details: detergent released, pronase digested
Biol. unit: Homo-Tetramer (from PDB file)
Resolution:
1.70Å     R-factor:   not given    
Authors: J.N.Varghese
Key ref:
J.N.Varghese et al. (1997). Structural evidence for a second sialic acid binding site in avian influenza virus neuraminidases. Proc Natl Acad Sci U S A, 94, 11808-11812. PubMed id: 9342319 DOI: 10.1073/pnas.94.22.11808
Date:
27-Aug-97     Release date:   04-Mar-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P03472  (NRAM_I75A5) -  Neuraminidase
Seq:
Struc: 		470 a.a.
388 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.2.1.18  - 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     membrane   1 term 
  Biological process     carbohydrate metabolic process   1 term 
  Biochemical function     exo-alpha-sialidase activity     1 term  

 

 
DOI no: 10.1073/pnas.94.22.11808 Proc Natl Acad Sci U S A 94:11808-11812 (1997)
PubMed id: 9342319  
 
 
Structural evidence for a second sialic acid binding site in avian influenza virus neuraminidases.
J.N.Varghese, P.M.Colman, A.van Donkelaar, T.J.Blick, A.Sahasrabudhe, J.L.McKimm-Breschkin.
 
  ABSTRACT  
 
The x-ray structure of a complex of sialic acid (Neu5Ac) with neuraminidase N9 subtype from A/tern/Australia/G70C/75 influenza virus at 4 degrees C has revealed the location of a second Neu5Ac binding site on the surface of the enzyme. At 18 degrees C, only the enzyme active site contains bound Neu5Ac. Neu5Ac binds in the second site in the chair conformation in a similar way to which it binds to hemagglutinin. The residues that interact with Neu5Ac at this second site are mostly conserved in avian strains, but not in human and swine strains, indicating that it has some as-yet-unknown biological function in birds.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. A molecular surface rendered image (42) of a tetrameric head of A/tern/Australia/G70C/75 N9 NA viewed from above the molecule. The active site residues interacting with the Neu5Ac moiety (twist-boat conformation) in the catalytic sites are show in green. The residues that interact with the Neu5Ac moiety (chair conformation) in the^ HB sites are colored yellow (conserved in all avian strains) and^ blue (conserved in N9 stains). (Inset) A magnified region (×1.6) in the vicinity of these two sites of one subunit, illustrating the deep pocket of the catalytic site and the flat surface of^ the HB site of the enzyme. 		Figure 2.
Fig. 2. (A) A stereo drawing (43) of the refined x-ray atomic model of the Neu5Ac (orange) bound in the HA site of A/tern/Australia/G70C/75^ NA with Neu5Ac soaked at 4°C, showing all the amino acids (green), and water molecules (red) making contact with the moiety. Atomic^ interactions are shown in broken lines. Oxygen, nitrogen, and^ carbon atoms are colored red, blue, and black, respectively. The^ protein backbone is represented by a yellow tube. (B) The two-F[o]-F[c]^ electron density map (blue caged-mesh contour at 1.6 level) of the Neu5Ac in the same orientation, using the refined phases of the complex, where F[o] and F[c] are the observed and calculated^ structure factors, respectively.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19939933 E.de Wit, V.J.Munster, D.van Riel, W.E.Beyer, G.F.Rimmelzwaan, T.Kuiken, A.D.Osterhaus, and R.A.Fouchier (2010).
Molecular determinants of adaptation of highly pathogenic avian influenza H7N7 viruses to efficient replication in the human host.
  J Virol, 84, 1597-1606.  
20155919 J.C.Sung, A.W.Van Wynsberghe, R.E.Amaro, W.W.Li, and J.A.McCammon (2010).
Role of secondary sialic acid binding sites in influenza N1 neuraminidase.
  J Am Chem Soc, 132, 2883-2885.  
20410266 Y.P.Lin, V.Gregory, P.Collins, J.Kloess, S.Wharton, N.Cattle, A.Lackenby, R.Daniels, and A.Hay (2010).
Neuraminidase receptor binding variants of human influenza A(H3N2) viruses resulting from substitution of aspartic acid 151 in the catalytic site: a role in virus attachment?
  J Virol, 84, 6769-6781.  
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.  
19390154 P.M.Dominiak, A.Volkov, A.P.Dominiak, K.N.Jarzembska, and P.Coppens (2009).
Combining crystallographic information and an aspherical-atom data bank in the evaluation of the electrostatic interaction energy in an enzyme-substrate complex: influenza neuraminidase inhibition.
  Acta Crystallogr D Biol Crystallogr, 65, 485-499.  
18558668 L.S.Cheng, R.E.Amaro, D.Xu, W.W.Li, P.W.Arzberger, and J.A.McCammon (2008).
Ensemble-based virtual screening reveals potential novel antiviral compounds for avian influenza neuraminidase.
  J Med Chem, 51, 3878-3894.  
18669647 X.Jing, C.Ma, Y.Ohigashi, F.A.Oliveira, T.S.Jardetzky, L.H.Pinto, and R.A.Lamb (2008).
Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel.
  Proc Natl Acad Sci U S A, 105, 10967-10972.  
17855542 H.L.Yen, N.A.Ilyushina, R.Salomon, E.Hoffmann, R.G.Webster, and E.A.Govorkova (2007).
Neuraminidase inhibitor-resistant recombinant A/Vietnam/1203/04 (H5N1) influenza viruses retain their replication efficiency and pathogenicity in vitro and in vivo.
  J Virol, 81, 12418-12426.  
17157891 U.B.Aamir, U.Wernery, N.Ilyushina, and R.G.Webster (2007).
Characterization of avian H9N2 influenza viruses from United Arab Emirates 2000 to 2003.
  Virology, 361, 45-55.  
16929094 B.J.Smith, T.Huyton, R.P.Joosten, J.L.McKimm-Breschkin, J.G.Zhang, C.S.Luo, M.Z.Lou, N.E.Labrou, and T.P.Garrett (2006).
Structure of a calcium-deficient form of influenza virus neuraminidase: implications for substrate binding.
  Acta Crystallogr D Biol Crystallogr, 62, 947-952.
PDB code: 2b8h
16575529 E.M.Rapoport, L.V.Mochalova, H.J.Gabius, J.Romanova, and N.V.Bovin (2006).
Search for additional influenza virus to cell interactions.
  Glycoconj J, 23, 115-125.  
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.  
15016893 V.Zaitsev, M.von Itzstein, D.Groves, M.Kiefel, T.Takimoto, A.Portner, and G.Taylor (2004).
Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: implications for fusion.
  J Virol, 78, 3733-3741.
PDB codes: 1usr 1usx
  10482558 C.F.Basler, A.García-Sastre, and P.Palese (1999).
Mutation of neuraminidase cysteine residues yields temperature-sensitive influenza viruses.
  J Virol, 73, 8095-8103.  
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 code is shown on the right.