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PDBsum entry 1f8b

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protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
1f8b
Jmol
Contents
Protein chain
388 a.a. *
Ligands
NAG-NAG-MAN-MAN-
MAN-MAN-MAN
NAG-NAG
NAG
DAN
Metals
_CA ×2
Waters ×346
* Residue conservation analysis
PDB id:
1f8b
Name: Hydrolase/hydrolase inhibitor
Title: Native influenza virus neuraminidase in complex with neu5ac2
Structure: Neuraminidase. Chain: a. Fragment: integral membrane protein, membrane stalk cleaved pronase releasing fully active residues 82-468.. Engineered: yes
Source: Influenza a virus (a/tern/australia/g70c/1975(h11n9)). Organism_taxid: 384509. Strain: a/tern/australia/g70c/75. Expressed in: influenza a virus. Expression_system_taxid: 11320.
Biol. unit: Tetramer (from PDB file)
Resolution:
1.80Å     R-factor:   0.166     R-free:   0.214
Authors: B.J.Smith,P.M.Colman,M.Von Itzstein,B.Danylec,J.N.Varghese
Key ref: B.J.Smith et al. (2001). Analysis of inhibitor binding in influenza virus neuraminidase. Protein Sci, 10, 689-696. PubMed id: 11274459
Date:
30-Jun-00     Release date:   11-Apr-01    
PROCHECK
Go to PROCHECK summary
 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  

 

 
Protein Sci 10:689-696 (2001)
PubMed id: 11274459  
 
 
Analysis of inhibitor binding in influenza virus neuraminidase.
B.J.Smith, P.M.Colman, M.Von Itzstein, B.Danylec, J.N.Varghese.
 
  ABSTRACT  
 
2,3-didehydro-2-deoxy-N:-acetylneuraminic acid (DANA) is a transition state analog inhibitor of influenza virus neuraminidase (NA). Replacement of the hydroxyl at the C9 position in DANA and 4-amino-DANA with an amine group, with the intention of taking advantage of an increased electrostatic interaction with a conserved acidic group in the active site to improve inhibitor binding, significantly reduces the inhibitor activity of both compounds. The three-dimensional X-ray structure of the complexes of these ligands and NA was obtained to 1.4 A resolution and showed that both ligands bind isosterically to DANA. Analysis of the geometry of the ammonium at the C4 position indicates that Glu119 may be neutral when these ligands bind. A computational analysis of the binding energies indicates that the substitution is successful in increasing the energy of interaction; however, the gains that are made are not sufficient to overcome the energy that is required to desolvate that part of the ligand that comes in contact with the protein.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21058397 S.Indu, V.Kochat, S.Thakurela, C.Ramakrishnan, and R.Varadarajan (2011).
Conformational analysis and design of cross-strand disulfides in antiparallel β-sheets.
  Proteins, 79, 244-260.  
19221587 K.Chen, and L.Kurgan (2009).
Investigation of atomic level patterns in protein--small ligand interactions.
  PLoS ONE, 4, e4473.  
19390154 P.M.Dominiak, A.Volkov, A.P.Dominiak, K.N.Jarzembska, and P.Coppens (2009).
Combining crystallographic information and an aspherical-atom data bank in the evaluation of the electrostatic interaction energy in an enzyme-substrate complex: influenza neuraminidase inhibition.
  Acta Crystallogr D Biol Crystallogr, 65, 485-499.  
19865756 Z.Yang, G.Yang, Y.Zu, Y.Fu, and L.Zhou (2009).
The conformational analysis and proton transfer of neuraminidase inhibitors: a theoretical study.
  Phys Chem Chem Phys, 11, 10035-10041.  
18074341 A.D.Hill, and P.J.Reilly (2008).
A Gibbs free energy correlation for automated docking of carbohydrates.
  J Comput Chem, 29, 1131-1141.  
17559075 Q.S.Du, R.B.Huang, Y.T.Wei, L.Q.Du, and K.C.Chou (2008).
Multiple field three dimensional quantitative structure-activity relationship (MF-3D-QSAR).
  J Comput Chem, 29, 211-219.  
17085491 O.Aruksakunwong, M.Malaisree, P.Decha, P.Sompornpisut, V.Parasuk, S.Pianwanit, and S.Hannongbua (2007).
On the lower susceptibility of oseltamivir to influenza neuraminidase subtype N1 than those in N2 and N9.
  Biophys J, 92, 798-807.  
16912325 H.L.Yen, E.Hoffmann, G.Taylor, C.Scholtissek, A.S.Monto, R.G.Webster, and E.A.Govorkova (2006).
Importance of neuraminidase active-site residues to the neuraminidase inhibitor resistance of influenza viruses.
  J Virol, 80, 8787-8795.  
16575530 M.C.Mann, T.Islam, J.C.Dyason, P.Florio, C.J.Trower, R.J.Thomson, and M.von Itzstein (2006).
Unsaturated N-acetyl- D-glucosaminuronic acid glycosides as inhibitors of influenza virus sialidase.
  Glycoconj J, 23, 127-133.  
17002371 N.Basdevant, H.Weinstein, and M.Ceruso (2006).
Thermodynamic basis for promiscuity and selectivity in protein-protein interactions: PDZ domains, a case study.
  J Am Chem Soc, 128, 12766-12777.  
15044728 P.Bonnet, and R.A.Bryce (2004).
Molecular dynamics and free energy analysis of neuraminidase-ligand interactions.
  Protein Sci, 13, 946-957.  
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.