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PDBsum entry 1bji

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Neuraminidase PDB id
1bji
Jmol
Contents
Protein chain
388 a.a. *
Ligands
NAG-NAG-BMA-MAN-
MAN-MAN
MAN
NAG ×2
DPC
Metals
_CA
Waters ×191
* Residue conservation analysis
PDB id:
1bji
Name: Neuraminidase
Title: The x-ray structure of a complex of tern n9 influenza virus neuraminidase complexed with the glaxo 6-carboxamide sialic analogue gr217029
Structure: Neuraminidase. Chain: a. Fragment: residues 82 - 468. Synonym: sialidase. Other_details: integral membrane protein, membrane bound st cleaved by pronase, releasing fully active head with residu 468
Source: Influenza a virus. Organism_taxid: 11320. Strain: a/tern/australia/g70c/75. Other_details: detergent released, pronase digested
Biol. unit: Homo-Tetramer (from PDB file)
Resolution:
2.00Å     R-factor:   0.155    
Authors: J.N.Varghese
Key ref: N.R.Taylor et al. (1998). Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of influenza virus sialidases. 2. Crystallographic and molecular modeling study of complexes of 4-amino-4H-pyran-6-carboxamides and sialidase from influenza virus types A and B. J Med Chem, 41, 798-807. PubMed id: 9526556 DOI: 10.1021/jm9703754
Date:
03-Dec-97     Release date:   03-Jun-98    
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  

 

 
DOI no: 10.1021/jm9703754 J Med Chem 41:798-807 (1998)
PubMed id: 9526556  
 
 
Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of influenza virus sialidases. 2. Crystallographic and molecular modeling study of complexes of 4-amino-4H-pyran-6-carboxamides and sialidase from influenza virus types A and B.
N.R.Taylor, A.Cleasby, O.Singh, T.Skarzynski, A.J.Wonacott, P.W.Smith, S.L.Sollis, P.D.Howes, P.C.Cherry, R.Bethell, P.Colman, J.Varghese.
 
  ABSTRACT  
 
The first paper in this series (see previous article) described structure-activity studies of carboxamide analogues of zanamivir binding to influenza virus sialidase types A and B and showed that inhibitory activity of these compounds was much greater against influenza A enzyme. To understand the large differences in affinities, a number of protein-ligand complexes have been investigated using crystallography and molecular dynamics. The crystallographic studies show that the binding of ligands containing tertiary amide groups is accompanied by the formation of an intramolecular planar salt bridge between two amino acid residues in the active site of the enzyme. It is proposed that the unexpected strong binding of these inhibitors is a result of the burial of hydrophobic surface area and salt-bridge formation in an environment of low dielectric. In sialidase from type A virus, binding of the carboxamide moeity and salt-bridge formation have only a minor effect on the positions of the surrounding residues, whereas in type B enzyme, significant distortion of the protein is observed. The results suggest that the decreased affinity in enzyme from influenza B is directly correlated with the small changes that occur in the amino acid residue interactions accompanying ligand binding. Molecular dynamics calculations have shown that the tendency for salt-bridge formation is greater in influenza A sialidase than influenza B sialidase and that this tendency is a useful descriptor for the prediction of inhibitor potency.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
23250062 P.M.Colman (2013).
Early days in drug discovery by crystallography - personal recollections.
  Acta Crystallogr A, 69, 60-62.  
22798847 S.K.Mohamed, M.Akkurt, M.N.Tahir, A.A.Abdelhamid, and S.H.Younes (2012).
2-Amino-4-(4-meth-oxy-phen-yl)-5-oxo-5,6,7,8-tetra-hydro-4H-chromene-3-carbonitrile 1,4-dioxane hemisolvate.
  Acta Crystallogr Sect E Struct Rep Online, 68, o2178-o2179.  
20695427 A.J.Oakley, S.Barrett, T.S.Peat, J.Newman, V.A.Streltsov, L.Waddington, T.Saito, M.Tashiro, and J.L.McKimm-Breschkin (2010).
Structural and functional basis of resistance to neuraminidase inhibitors of influenza B viruses.
  J Med Chem, 53, 6421-6431.
PDB codes: 3k36 3k37 3k38 3k39 3k3a
20345171 C.Bissantz, B.Kuhn, and M.Stahl (2010).
A medicinal chemist's guide to molecular interactions.
  J Med Chem, 53, 5061-5084.  
20213331 J.Sun, S.Cai, H.Mei, J.Li, N.Yan, and Y.Wang (2010).
Docking and 3D QSAR study of thiourea analogs as potent inhibitors of influenza virus neuraminidase.
  J Mol Model, 16, 1809-1818.  
20512460 M.M.Ramiz, W.A.El-Sayed, A.I.El-Tantawy, and A.A.Abdel-Rahman (2010).
Antimicrobial activity of new 4,6-disubstituted pyrimidine, pyrazoline, and pyran derivatives.
  Arch Pharm Res, 33, 647-654.  
20808434 R.Patil, S.Das, A.Stanley, L.Yadav, A.Sudhakar, and A.K.Varma (2010).
Optimized hydrophobic interactions and hydrogen bonding at the target-ligand interface leads the pathways of drug-designing.
  PLoS One, 5, 0.  
  19923724 I.Campeotto, S.B.Carr, C.H.Trinh, A.S.Nelson, A.Berry, S.E.Phillips, and A.R.Pearson (2009).
Structure of an Escherichia coli N-acetyl-D-neuraminic acid lyase mutant, E192N, in complex with pyruvate at 1.45 angstrom resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 1088-1090.
PDB code: 2wkj
19950979 J.L.Paulsen, and A.C.Anderson (2009).
Scoring ensembles of docked protein:ligand interactions for virtual lead optimization.
  J Chem Inf Model, 49, 2813-2819.  
19254207 P.M.Colman (2009).
New antivirals and drug resistance.
  Annu Rev Biochem, 78, 95.  
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.  
18230325 A.Bolt, A.Berry, and A.Nelson (2008).
Directed evolution of aldolases for exploitation in synthetic organic chemistry.
  Arch Biochem Biophys, 474, 318-330.  
17939760 A.Moscona (2008).
Medical management of influenza infection.
  Annu Rev Med, 59, 397-413.  
18612831 D.C.Thompson, R.A.Denny, R.Nilakantan, C.Humblet, D.Joseph-McCarthy, and E.Feyfant (2008).
CONFIRM: connecting fragments found in receptor molecules.
  J Comput Aided Mol Des, 22, 761-772.  
18061879 M.A.Lill (2007).
Multi-dimensional QSAR in drug discovery.
  Drug Discov Today, 12, 1013-1017.  
17597592 Y.Lu, and J.Gervay-Hague (2007).
Synthesis of C-4 and C-7 triazole analogs of zanamivir as multivalent sialic acid containing scaffolds.
  Carbohydr Res, 342, 1636-1650.  
16929094 B.J.Smith, T.Huyton, R.P.Joosten, J.L.McKimm-Breschkin, J.G.Zhang, C.S.Luo, M.Z.Lou, N.E.Labrou, and T.P.Garrett (2006).
Structure of a calcium-deficient form of influenza virus neuraminidase: implications for substrate binding.
  Acta Crystallogr D Biol Crystallogr, 62, 947-952.
PDB code: 2b8h
17016746 J.K.Shepphird, and R.D.Clark (2006).
A marriage made in torsional space: using GALAHAD models to drive pharmacophore multiplet searches.
  J Comput Aided Mol Des, 20, 763-771.  
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.  
16915238 M.Luo (2006).
Structural biology: antiviral drugs fit for a purpose.
  Nature, 443, 37-38.
PDB codes: 2htr 2hty 2hu0 2hu4
17005277 T.L.Sorensen, K.E.McAuley, R.Flaig, and E.M.Duke (2006).
New light for science: synchrotron radiation in structural medicine.
  Trends Biotechnol, 24, 500-508.  
16204883 J.S.Finer-Moore, A.C.Anderson, R.H.O'Neil, M.P.Costi, S.Ferrari, J.Krucinski, and R.M.Stroud (2005).
The structure of Cryptococcus neoformans thymidylate synthase suggests strategies for using target dynamics for species-specific inhibition.
  Acta Crystallogr D Biol Crystallogr, 61, 1320-1334.
PDB codes: 2a9w 2aaz
16149103 L.Ying, and J.Gervay-Hague (2005).
One-bead-one-inhibitor-one-substrate screening of neuraminidase activity.
  Chembiochem, 6, 1857-1865.  
15918777 P.M.Colman (2005).
Zanamivir: an influenza virus neuraminidase inhibitor.
  Expert Rev Anti Infect Ther, 3, 191-199.  
15858666 T.Woodhall, G.Williams, A.Berry, and A.Nelson (2005).
Synthesis of screening substrates for the directed evolution of sialic acid aldolase: towards tailored enzymes for the preparation of influenza A sialidase inhibitor analogues.
  Org Biomol Chem, 3, 1795-1800.  
15742315 T.Woodhall, G.Williams, A.Berry, and A.Nelson (2005).
Creation of a tailored aldolase for the parallel synthesis of sialic acid mimetics.
  Angew Chem Int Ed Engl, 44, 2109-2112.  
15159560 B.S.Lommer, S.M.Ali, S.N.Bajpai, W.J.Brouillette, G.M.Air, and M.Luo (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.
PDB codes: 1uja 1vcj
15211517 T.Haselhorst, J.C.Wilson, R.J.Thomson, S.McAtamney, J.G.Menting, R.L.Coppel, and M.von Itzstein (2004).
Saturation transfer difference (STD) 1H-NMR experiments and in silico docking experiments to probe the binding of N-acetylneuraminic acid and derivatives to Vibrio cholerae sialidase.
  Proteins, 56, 346-353.  
12838268 S.J.Teague (2003).
Implications of protein flexibility for drug discovery.
  Nat Rev Drug Discov, 2, 527-541.  
11829724 J.L.McKimm-Breschkin (2002).
Neuraminidase inhibitors for the treatment and prevention of influenza.
  Expert Opin Pharmacother, 3, 103-112.  
11983568 M.B.Swindells, and J.P.Overington (2002).
Prioritizing the proteome: identifying pharmaceutically relevant targets.
  Drug Discov Today, 7, 516-521.  
11274459 B.J.Smith, P.M.Colman, M.Von Itzstein, B.Danylec, and J.N.Varghese (2001).
Analysis of inhibitor binding in influenza virus neuraminidase.
  Protein Sci, 10, 689-696.
PDB codes: 1f8b 1f8c 1f8d 1f8e
11709315 L.V.Gubareva, R.G.Webster, and F.G.Hayden (2001).
Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants.
  Antimicrob Agents Chemother, 45, 3403-3408.  
11257030 S.Bantia, C.D.Parker, S.L.Ananth, L.L.Horn, K.Andries, P.Chand, P.L.Kotian, A.Dehghani, Y.El-Kattan, T.Lin, T.L.Hutchison, J.A.Montgomery, D.L.Kellog, and Y.S.Babu (2001).
Comparison of the anti-influenza virus activity of RWJ-270201 with those of oseltamivir and zanamivir.
  Antimicrob Agents Chemother, 45, 1162-1167.  
10853664 Q.Wang, M.Wolff, T.Polat, Y.Du, and R.J.Linhardt (2000).
Inhibition of neuraminidase with neuraminic acid C-glycosides.
  Bioorg Med Chem Lett, 10, 941-944.  
10098672 P.W.Smith, J.E.Robinson, D.N.Evans, S.L.Sollis, P.D.Howes, N.Trivedi, and R.C.Bethell (1999).
Sialidase inhibitors related to zanamivir: synthesis and biological evaluation of 4H-pyran 6-ether and ketone.
  Bioorg Med Chem Lett, 9, 601-604.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.