PDBsum entry 1nna

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Hydrolase(o-glycosyl) PDB id
Protein chain
387 a.a. *
* Residue conservation analysis
PDB id:
Name: Hydrolase(o-glycosyl)
Title: Three-dimensional structure of influenza a n9 neuraminidase complex with the inhibitor 2-deoxy 2,3-dehydro-n-acetyl neu acid
Structure: Neuraminidase. Chain: a. Engineered: yes
Source: Influenza a virus. Organism_taxid: 11320. Strain: a/tern/australia/g70c/75 h11n9. Cell_line: s2
Biol. unit: Tetramer (from PQS)
2.50Å     R-factor:   0.193    
Authors: P.Bossart-Whitaker,M.Carson,Y.S.Babu,C.D.Smith,W.G.Laver,G.M
Key ref: P.Bossart-Whitaker et al. (1993). Three-dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydro-N-acetyl neuraminic acid. J Mol Biol, 232, 1069-1083. PubMed id: 8371267
08-Mar-93     Release date:   30-Apr-94    
Go to PROCHECK summary

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

 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 232:1069-1083 (1993)
PubMed id: 8371267  
Three-dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydro-N-acetyl neuraminic acid.
P.Bossart-Whitaker, M.Carson, Y.S.Babu, C.D.Smith, W.G.Laver, G.M.Air.
We present here the three-dimensional structure of neuraminidase (E.C. from influenza virus A/Tern/Australia/G70c/75 (N9), determined by the method of multiple isomorphous replacement, and the structure of the neuraminidase complexed with an inhibitor, 2-deoxy-2,3-dehydro-N-acetyl neuraminic acid (DANA). Native and inhibitor complex crystals are isomorphous and belong to space group I432 with unit cell dimensions of 183.78 A. The native enzyme structure and the inhibitor complex structure have been refined at 2.5 A and 2.8 A resolution, respectively, with crystallographic R-factor values of 0.193 for the native enzyme, and 0.179 for the inhibitor complex. The current enzyme model includes 387 amino acid residues which comprise the asymmetric unit. The root-mean-square deviation from ideal values is 0.013 A for bond lengths and 1.6 degree for bond angles. The neuraminidase (NA), as proteolytically cleaved from the virus, retains full enzymatic and antigenic activity, and is a box-shaped tetramer with edge lengths of 90 A and a maximal depth of 60 A. The NA tetramers are composed of crystallographically equivalent monomers related by circular 4-fold symmetry. Each monomer folds into six antiparallel beta-sheets of four strands. The secondary structure composition is 50% beta-sheet. The remaining 50% of the residues form 24 strand-connecting loops or turns. One of the loops contains a small alpha-helix. The structure of the complex of NA with DANA, a transition state analog, has enabled us to identify and characterize the site of enzyme catalysis. The center of mass of bound inhibitor is 32 A from the 4-fold axis of the tetramer, lodged at the end of a shallow crater of diameter 16 A with a depth of 8 to 10 A. There are 12 amino acid residues that directly bind DANA, with a further six conserved amino acids lining the active site pocket. The neuraminidase inhibitor complex provides a three-dimensional model which will be used to further the understanding of enzymatic hydrolysis and aid the design of specific, antineuraminidase antiviral compounds.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21382719 Y.Liu, F.Jing, Y.Xu, Y.Xie, F.Shi, H.Fang, M.Li, and W.Xu (2011).
Design, synthesis and biological activity of thiazolidine-4-carboxylic acid derivatives as novel influenza neuraminidase inhibitors.
  Bioorg Med Chem, 19, 2342-2348.  
20941447 H.Ge, Y.F.Wang, J.Xu, Q.Gu, H.B.Liu, P.G.Xiao, J.Zhou, Y.Liu, Z.Yang, and H.Su (2010).
Anti-influenza agents from Traditional Chinese Medicine.
  Nat Prod Rep, 27, 1758-1780.  
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.  
19855826 W.C.Van Voorhis, W.G.Hol, P.J.Myler, and L.J.Stewart (2009).
The role of medical structural genomics in discovering new drugs for infectious diseases.
  PLoS Comput Biol, 5, e1000530.
PDB codes: 3eiy 3ej0
17426694 C.Y.Li, Q.Yu, Z.Q.Ye, Y.Sun, Q.He, X.M.Li, W.Zhang, J.Luo, X.Gu, X.Zheng, and L.Wei (2007).
A nonsynonymous SNP in human cytosolic sialidase in a small Asian population results in reduced enzyme activity: potential link with severe adverse reactions to oseltamivir.
  Cell Res, 17, 357-362.  
16915235 R.J.Russell, L.F.Haire, D.J.Stevens, P.J.Collins, Y.P.Lin, G.M.Blackburn, A.J.Hay, S.J.Gamblin, and J.J.Skehel (2006).
The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design.
  Nature, 443, 45-49.
PDB codes: 2ht5 2ht7 2ht8 2htq 2htr 2htu 2htv 2htw 2hty 2hu0 2hu4
15967977 C.C.Hsu, Z.Hong, M.Wada, D.Franke, and C.H.Wong (2005).
Directed evolution of D-sialic acid aldolase to L-3-deoxy-manno-2-octulosonic acid (L-KDO) aldolase.
  Proc Natl Acad Sci U S A, 102, 9122-9126.  
15911320 P.Chand, S.Bantia, P.L.Kotian, Y.El-Kattan, T.H.Lin, and Y.S.Babu (2005).
Comparison of the anti-influenza virus activity of cyclopentane derivatives with oseltamivir and zanamivir in vivo.
  Bioorg Med Chem, 13, 4071-4077.  
15159560 B.S.Lommer, S.M.Ali, S.N.Bajpai, W.J.Brouillette, G.M.Air, and M.Luo (2004).
A benzoic acid inhibitor induces a novel conformational change in the active site of Influenza B virus neuraminidase.
  Acta Crystallogr D Biol Crystallogr, 60, 1017-1023.
PDB codes: 1uja 1vcj
11991966 A.Molla, W.Kati, R.Carrick, K.Steffy, Y.Shi, D.Montgomery, N.Gusick, V.S.Stoll, K.D.Stewart, T.I.Ng, C.Maring, D.J.Kempf, and W.Kohlbrenner (2002).
In vitro selection and characterization of influenza A (A/N9) virus variants resistant to a novel neuraminidase inhibitor, A-315675.
  J Virol, 76, 5380-5386.  
12435681 M.Z.Wang, C.Y.Tai, and D.B.Mendel (2002).
Mechanism by which mutations at his274 alter sensitivity of influenza a virus n1 neuraminidase to oseltamivir carboxylate and zanamivir.
  Antimicrob Agents Chemother, 46, 3809-3816.  
11779391 D.Young, C.Fowler, and K.Bush (2001).
RWJ-270201 (BCX-1812): a novel neuraminidase inhibitor for influenza.
  Philos Trans R Soc Lond B Biol Sci, 356, 1905-1913.  
11557461 E.A.Govorkova, I.A.Leneva, O.G.Goloubeva, K.Bush, and R.G.Webster (2001).
Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses.
  Antimicrob Agents Chemother, 45, 2723-2732.  
  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.  
8877699 M.Carson (1996).
Wavelets and molecular structure.
  J Comput Aided Mol Des, 10, 273-283.  
8591030 A.Gaskell, S.Crennell, and G.Taylor (1995).
The three domains of a bacterial sialidase: a beta-propeller, an immunoglobulin module and a galactose-binding jelly-roll.
  Structure, 3, 1197-1205.
PDB codes: 1eur 1eus 1eut 1euu
  7549872 J.N.Varghese, V.C.Epa, and P.M.Colman (1995).
Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase.
  Protein Sci, 4, 1081-1087.
PDB codes: 1nnc 7nn9
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
7876189 S.L.Edwards, V.L.Davidson, Y.L.Hyun, and P.T.Wingfield (1995).
Spectroscopic evidence for a common electron transfer pathway for two tryptophan tryptophylquinone enzymes.
  J Biol Chem, 270, 4293-4298.  
7712292 J.D.McCarter, and S.G.Withers (1994).
Mechanisms of enzymatic glycoside hydrolysis.
  Curr Opin Struct Biol, 4, 885-892.  
7922030 S.Crennell, E.Garman, G.Laver, E.Vimr, and G.Taylor (1994).
Crystal structure of Vibrio cholerae neuraminidase reveals dual lectin-like domains in addition to the catalytic domain.
  Structure, 2, 535-544.
PDB code: 1kit
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.