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PDBsum entry 1ing

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protein ligands metals Protein-protein interface(s) links
Hydrolase (o-glycosyl) PDB id
1ing
Jmol
Contents
Protein chains
388 a.a. *
Ligands
NAG-NAG ×4
NAG-NAG-BMA-FUL
NAG-NAG-BMA-MAN-
MAN-MAN
×2
ST5 ×2
NAG-NAG-BMA-FUC
Metals
_CA ×2
Waters ×750
* Residue conservation analysis
PDB id:
1ing
Name: Hydrolase (o-glycosyl)
Title: Influenza a subtype n2 neuraminidase complexed with aromatic inhibitor
Structure: Influenza a subtype n2 neuraminidase. Chain: a, b. Synonym: sialidase. Ec: 3.2.1.18
Source: Influenza a virus. Organism_taxid: 11320. Strain: a/tokyo/3/67
Biol. unit: Tetramer (from PQS)
Resolution:
2.40Å     R-factor:   0.163    
Authors: M.J.Jedrzejas,M.Luo
Key ref: S.Singh et al. (1995). Structure-based inhibitors of influenza virus sialidase. A benzoic acid lead with novel interaction. J Med Chem, 38, 3217-3225. PubMed id: 7650674 DOI: 10.1021/jm00017a005
Date:
07-Jul-95     Release date:   17-Aug-96    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P06820  (NRAM_I67A0) -  Neuraminidase
Seq:
Struc:
469 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.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   3 terms 
  Biological process     carbohydrate metabolic process   1 term 
  Biochemical function     exo-alpha-sialidase activity     1 term  

 

 
DOI no: 10.1021/jm00017a005 J Med Chem 38:3217-3225 (1995)
PubMed id: 7650674  
 
 
Structure-based inhibitors of influenza virus sialidase. A benzoic acid lead with novel interaction.
S.Singh, M.J.Jedrzejas, G.M.Air, M.Luo, W.G.Laver, W.J.Brouillette.
 
  ABSTRACT  
 
Influenza virus sialidase is a surface enzyme that is essential for infection of the virus. The catalytic site is highly conserved among all known influenza variants, suggesting that this protein is a suitable target for drug intervention. The most potent known inhibitors are analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en), particularly the 4-guanidino derivative (4-guanidino-Neu5Ac2en). We utilized the benzene ring of 4-(N-acetylamino)benzoic acids as a cyclic template to substitute for the dihydropyran ring of Neu5Ac2en. In this study several 3-(N-acylamino) derivatives were prepared as potential replacements for the glycerol side chain of Neu5Ac2en, and some were found to interact with the same binding subsite of sialidase. Of greater significance was the observation that the 3-guanidinobenzoic acid derivative (equivalent to the 4-guanidino grouping of 4-guanidino-Neu5Ac2en), the most potent benzoic acid inhibitor of influenza sialidase thus far identified (IC50 = 10 microM), occupied the glycerol-binding subsite on sialidase as opposed to the guanidino-binding subsite. This benzoic acid derivative thus provides a new compound that interacts in a novel manner with the catalytic site of influenza sialidase.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
11274459 B.J.Smith, P.M.Colman, M.Von Itzstein, B.Danylec, and J.N.Varghese (2001).
Analysis of inhibitor binding in influenza virus neuraminidase.
  Protein Sci, 10, 689-696.
PDB codes: 1f8b 1f8c 1f8d 1f8e
10450950 W.J.Brouillette, V.R.Atigadda, M.Luo, G.M.Air, Y.S.Babu, and S.Bantia (1999).
Design of benzoic acid inhibitors of influenza neuraminidase containing a cyclic substitution for the N-acetyl grouping.
  Bioorg Med Chem Lett, 9, 1901-1906.  
  9559786 S.Bantia, A.A.Ghate, S.L.Ananth, Y.S.Babu, G.M.Air, and G.M.Walsh (1998).
Generation and characterization of a mutant of influenza A virus selected with the neuraminidase inhibitor BCX-140.
  Antimicrob Agents Chemother, 42, 801-807.  
15989515 R.C.Bethell, and P.W.Smith (1997).
Sialidase as a target for inhibitors of influenza virus replication.
  Expert Opin Investig Drugs, 6, 1501-1509.  
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.  
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.