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PDBsum entry 3w09

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protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
3w09
Jmol
Contents
Protein chain
388 a.a.
Ligands
NAG-NAG-BMA-MAN-
MAN-MAN-MAN-MAN-
MAN
NAG-NAG
NAG
GOL ×7
ZGE
Metals
_CA
Waters ×383
PDB id:
3w09
Name: Hydrolase/hydrolase inhibitor
Title: Influenza virus neuraminidase subtype n9 (tern) complexed wi guanidino-neu5ac2en inhibitor
Structure: Neuraminidase. Chain: a. Synonym: neuraminidase n9, sialidase, hydrolase(o-glycosyl) ec: 3.2.1.18
Source: Influenza a virus. Organism_taxid: 384509. Strain: a/tern/australia/g70c/1975(h11n9)
Resolution:
2.00Å     R-factor:   0.146     R-free:   0.189
Authors: V.A.Streltsov
Key ref: J.H.Kim et al. (2013). Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity. Science, 340, 71-75. PubMed id: 23429702 DOI: 10.1126/science.1232552
Date:
25-Oct-12     Release date:   01-May-13    
PROCHECK
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 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   3 terms 
  Biological process     carbohydrate metabolic process   1 term 
  Biochemical function     exo-alpha-sialidase activity     1 term  

 

 
DOI no: 10.1126/science.1232552 Science 340:71-75 (2013)
PubMed id: 23429702  
 
 
Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity.
J.H.Kim, R.Resende, T.Wennekes, H.M.Chen, N.Bance, S.Buchini, A.G.Watts, P.Pilling, V.A.Streltsov, M.Petric, R.Liggins, S.Barrett, J.L.McKimm-Breschkin, M.Niikura, S.G.Withers.
 
  ABSTRACT  
 
Influenza antiviral agents play important roles in modulating disease severity and in controlling pandemics while vaccines are prepared, but the development of resistance to agents like the commonly used neuraminidase inhibitor oseltamivir may limit their future utility. We report here on a new class of specific, mechanism-based anti-influenza drugs that function through the formation of a stabilized covalent intermediate in the influenza neuraminidase enzyme, and we confirm this mode of action with structural and mechanistic studies. These compounds function in cell-based assays and in animal models, with efficacies comparable to that of the neuraminidase inhibitor zanamivir and with broad-spectrum activity against drug-resistant strains in vitro. The similarity of their structure to that of the natural substrate and their mechanism-based design make these attractive antiviral candidates.