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PDBsum entry 4mju

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protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
4mju
Jmol
Contents
Protein chain
389 a.a.
Ligands
27S
Metals
_CA
Waters ×284
PDB id:
4mju
Name: Hydrolase/hydrolase inhibitor
Title: Influenza neuraminidase in complex with a novel antiviral co
Structure: Neuraminidase. Chain: a. Fragment: unp residues 81-469. Ec: 3.2.1.18
Source: Influenza a virus. Organism_taxid: 385580. Strain: a/duck/ukraine/1/1963 (h3n8)
Resolution:
2.35Å     R-factor:   0.186     R-free:   0.234
Authors: P.S.Kerry
Key ref: S.Mohan et al. (2014). Serendipitous discovery of a potent influenza virus a neuraminidase inhibitor. Angew Chem Int Ed Engl, 53, 1076-1080. PubMed id: 24339250 DOI: 10.1002/anie.201308142
Date:
04-Sep-13     Release date:   15-Jan-14    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q07599  (NRAM_I63A3) -  Neuraminidase
Seq:
Struc:
470 a.a.
389 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 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: 10.1002/anie.201308142 Angew Chem Int Ed Engl 53:1076-1080 (2014)
PubMed id: 24339250  
 
 
Serendipitous discovery of a potent influenza virus a neuraminidase inhibitor.
S.Mohan, P.S.Kerry, N.Bance, M.Niikura, B.M.Pinto.
 
  ABSTRACT  
 
We have previously reported a potent neuraminidase inhibitor that comprises a carbocyclic analogue of zanamivir in which the hydrophilic glycerol side chain is replaced by the hydrophobic 3-pentyloxy group of oseltamivir. This hybrid inhibitor showed excellent inhibitory properties in the neuraminidase inhibition assay (Ki =0.46 nM; Ki (zanamivir) =0.16 nM) and in the viral replication inhibition assay in cell culture at 10(-8)  M. As part of this lead optimization, we now report a novel spirolactam that shows comparable inhibitory activity in the cell culture assay to that of our lead compound at 10(-7)  M. The compound was discovered serendipitously during the attempted synthesis of the isothiourea derivative of the original candidate. The X-ray crystal structure of the spirolactam in complex with the N8 subtype neuraminidase offers insight into the mode of inhibition.