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PDBsum entry 4gb1

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protein ligands metals links
Hydrolase PDB id
4gb1
Jmol
Contents
Protein chain
387 a.a.
Ligands
0LP
Metals
_CA
Waters ×118
PDB id:
4gb1
Name: Hydrolase
Title: Synthesis and evaluation of novel 3-c-alkylated-neu5ac2en de as probes of influenza virus sialidase 150-loop flexibility
Structure: Neuraminidase. Chain: a. Fragment: unp residues 81-470. Ec: 3.2.1.18
Source: Influenza a virus. Organism_taxid: 385580. Strain: a/duck/ukraine/1/63 (h3n8)
Resolution:
2.62Å     R-factor:   0.208     R-free:   0.280
Authors: P.S.Kerry,S.Rudrawar,M-A.Rameix-Welti,A.Maggioni,J.C.Dyason, S.Van Der Werf,R.J.Thomson,N.Naffakh,R.J.M.Russell,M.Von It
Key ref: S.Rudrawar et al. (2012). Synthesis and evaluation of novel 3-C-alkylated-Neu5Ac2en derivatives as probes of influenza virus sialidase 150-loop flexibility. Org Biomol Chem, 10, 8628-8639. PubMed id: 22976385 DOI: 10.1039/c2ob25627d
Date:
26-Jul-12     Release date:   26-Sep-12    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q07599  (NRAM_I63A3) -  Neuraminidase
Seq:
Struc:
470 a.a.
387 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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: 10.1039/c2ob25627d Org Biomol Chem 10:8628-8639 (2012)
PubMed id: 22976385  
 
 
Synthesis and evaluation of novel 3-C-alkylated-Neu5Ac2en derivatives as probes of influenza virus sialidase 150-loop flexibility.
S.Rudrawar, P.S.Kerry, M.A.Rameix-Welti, A.Maggioni, J.C.Dyason, F.J.Rose, S.van der Werf, R.J.Thomson, N.Naffakh, R.J.Russell, M.von Itzstein.
 
  ABSTRACT  
 
Novel 3-C-alkylated-Neu5Ac2en derivatives have been designed to target the expanded active site cavity of influenza virus sialidases with an open 150-loop, currently seen in X-ray crystal structures of influenza A virus group-1 (N1, N4, N5, N8), but not group-2 (N2, N9), sialidases. The compounds show selectivity for inhibition of H5N1 and pdm09 H1N1 sialidases over an N2 sialidase, providing evidence of the relative 150-loop flexibility of these sialidases. In a complex with N8 sialidase, the C3 substituent of 3-phenylally-Neu5Ac2en occupies the 150-cavity while the central ring and the remaining substituents bind the active site as seen for the unsubstituted template. This new class of inhibitors, which can 'trap' the open 150-loop form of the sialidase, should prove useful as probes of 150-loop flexibility.