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PDBsum entry 1vcj

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protein ligands links
Hydrolase PDB id
1vcj
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Contents
Protein chain
389 a.a.
Ligands
IBA
Waters ×106
PDB id:
1vcj
Name: Hydrolase
Title: Influenza b virus neuraminidase complexed with 1-(4-carboxy- pentylamino)phenyl)-5-aminomethyl-5-hydroxymethyl-pyrrolidi
Structure: Neuraminidase. Chain: a. Fragment: catalytic domain residues 78-466. Ec: 3.2.1.18
Source: Influenza b virus (b/lee/40). Organism_taxid: 107412. Strain: b-lee-40
Biol. unit: Tetramer (from PDB file)
Resolution:
2.40Å     R-factor:   0.214     R-free:   0.255
Authors: B.S.Lommer,S.M.Ali,S.N.Bajpai,W.J.Brouillette,G.M.Air,M.Luo
Key ref:
B.S.Lommer et al. (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. PubMed id: 15159560 DOI: 10.1107/S0907444904006225
Date:
09-Mar-04     Release date:   23-Mar-04    
Supersedes: 1uja
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P03474  (NRAM_INBLE) -  Neuraminidase
Seq:
Struc:
466 a.a.
389 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: 10.1107/S0907444904006225 Acta Crystallogr D Biol Crystallogr 60:1017-1023 (2004)
PubMed id: 15159560  
 
 
A benzoic acid inhibitor induces a novel conformational change in the active site of Influenza B virus neuraminidase.
B.S.Lommer, S.M.Ali, S.N.Bajpai, W.J.Brouillette, G.M.Air, M.Luo.
 
  ABSTRACT  
 
Owing to the highly conserved nature of its active site, Influenza B virus neuraminidase (NA) has emerged as a major target for the design of novel anti-influenza drugs. A benzene-ring scaffold has been used in place of the pyranose ring of sialic acid to develop simpler NA inhibitors that contain a minimal number of chiral centers. A new compound belonging to this series, BANA 207, showed significant improvement in inhibitory activity against Influenza B virus NA compared with its parent compound. Here, the structural analysis of a complex of BANA 207 with influenza virus B/Lee/40 NA is reported. The results indicate that BANA 207 forms an unexpected interaction with the crucial active-site residue Glu275 that stabilizes the side chain of this residue in a conformation previously unobserved in NA-inhibitor complexes. This change in the side-chain orientation of Glu275 alters the topology of the triglycerol pocket, which accommodates an additional lipophilic substitution at the benzene ring and may provide an explanation for the increased activity of BANA 207 against Influenza B virus NA.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Chemical structures of (a) BANA 207 and (b) BANA 206.
Figure 4.
Figure 4 Stereoview of a F[o] - F[c] omit map of Glu275 contoured at 2.5 . Green, orientation of the side chain of Glu275 in the starting model (B/Lee/40 NA complexed with sialic acid). Red, fit of Glu275 to the density in the final model of the BANA 207-B/Lee/40 NA complex. A new water molecule is found near the former position of the Glu275 carboxyl group that forms hydrogen-bond interactions with His273 and Arg223. Both Glu275 and the water molecule were omitted for calculation of the electron density shown.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2004, 60, 1017-1023) copyright 2004.  
  Figures were selected by an automated process.  

 

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