PDBsum entry 1iny

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Hydrolase PDB id
Protein chain
388 a.a. *
NAG ×2
Waters ×165
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: A sialic acid derived phosphonate analog inhibits different influenza virus neuraminidase with different efficiencies
Structure: Influenza a subtype n9 neuraminidase. Chain: a. Engineered: yes
Source: Influenza a virus. Organism_taxid: 11320
Biol. unit: Tetramer (from PQS)
2.40Å     R-factor:   0.187    
Authors: C.L.White,M.N.Janakiraman,W.G.Laver,C.Philippon,A.Vasella,G. M.Luo
Key ref: C.L.White et al. (1995). A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies. J Mol Biol, 245, 623-634. PubMed id: 7844831
26-Sep-94     Release date:   07-Feb-95    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P03472  (NRAM_I75A5) -  Neuraminidase
470 a.a.
388 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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     membrane   3 terms 
  Biological process     carbohydrate metabolic process   1 term 
  Biochemical function     exo-alpha-sialidase activity     1 term  


J Mol Biol 245:623-634 (1995)
PubMed id: 7844831  
A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies.
C.L.White, M.N.Janakiraman, W.G.Laver, C.Philippon, A.Vasella, G.M.Air, M.Luo.
A phosphonate analog of N-acetyl neuraminic acid (PANA) has been designed as a potential neuraminidase (NA) inhibitor and synthesized as both the alpha (ePANA) and beta (aPANA) anomers. Inhibition of type A (N2) and type B NA activity by ePANA was approximately a 100-fold better than by sialic acid, but inhibition of type A (N9) NA was only ten-fold better than by sialic acid. The aPANA compound was not a strong inhibitor for any of the NA strains tested. The crystal structures at 2.4 A resolution of ePANA complexed to type A (N2) NA, type A (N9) NA and type B NA and aPANA complexed to type A (N2) NA showed that neither of the PANA compounds distorted the NA active site upon binding. No significant differences in the NA-ePANA complex structures were found to explain the anomalous inhibition of N9 neuraminidase by ePANA. We put forward the hypothesis that an increase in the ePANA inhibition compared to that caused by sialic acid is due to (1) a stronger electrostatic interaction between the inhibitor phosphonyl group and the active site arginine pocket and (2) a lower distortion energy requirement for binding of ePANA.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
15980456 A.Bohne-Lang, and C.W.von der Lieth (2005).
GlyProt: in silico glycosylation of proteins.
  Nucleic Acids Res, 33, W214-W219.  
15864320 J.N.Watson, T.L.Knoll, J.H.Chen, D.T.Chou, T.J.Borgford, and A.J.Bennet (2005).
Use of conformationally restricted pyridinium alpha-D-N-acetylneuraminides to probe specificity in bacterial and viral sialidases.
  Biochem Cell Biol, 83, 115-122.  
  9517945 D.B.Mendel, C.Y.Tai, P.A.Escarpe, W.Li, R.W.Sidwell, J.H.Huffman, C.Sweet, K.J.Jakeman, J.Merson, S.A.Lacy, W.Lew, M.A.Williams, L.Zhang, M.S.Chen, N.Bischofberger, and C.U.Kim (1998).
Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infection.
  Antimicrob Agents Chemother, 42, 640-646.  
  9094607 L.V.Gubareva, M.J.Robinson, R.C.Bethell, and R.G.Webster (1997).
Catalytic and framework mutations in the neuraminidase active site of influenza viruses that are resistant to 4-guanidino-Neu5Ac2en.
  J Virol, 71, 3385-3390.  
9331424 R.C.Wade (1997).
'Flu' and structure-based drug design.
  Structure, 5, 1139-1145.  
8994884 G.Taylor (1996).
Sialidases: structures, biological significance and therapeutic potential.
  Curr Opin Struct Biol, 6, 830-837.  
8913694 M.von Itzstein, and P.Colman (1996).
Design and synthesis of carbohydrate-based inhibitors of protein-carbohydrate interactions.
  Curr Opin Struct Biol, 6, 703-709.  
8879557 W.Fitz, P.B.Rosenthal, and C.H.Wong (1996).
Synthesis and inhibitory properties of a thiomethylmercuric sialic acid with application to the X-ray structure determination of 9-O-acetylsialic acid esterase from influenza C virus.
  Bioorg Med Chem, 4, 1349-1353.  
8592707 M.J.Jedrzejas, S.Singh, W.J.Brouillette, G.M.Air, and M.Luo (1995).
A strategy for theoretical binding constant, Ki, calculations for neuraminidase aromatic inhibitors designed on the basis of the active site structure of influenza virus neuraminidase.
  Proteins, 23, 264-277.
PDB code: 1ing
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