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PDBsum entry 1nsc

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protein ligands metals Protein-protein interface(s) links
Hydrolase(o-glycosyl) PDB id
1nsc
Jmol
Contents
Protein chains
390 a.a.
Ligands
NAG ×2
SIA ×2
Metals
_CA ×3
Waters ×1510
PDB id:
1nsc
Name: Hydrolase(o-glycosyl)
Title: Influenza b virus neuraminidase can synthesize its own inhib
Structure: Neuraminidase. Chain: a, b. Engineered: yes
Source: Influenza b virus (strain b/beijing/1/ organism_taxid: 11525. Strain: b/beijing/1/87
Biol. unit: Tetramer (from PQS)
Resolution:
1.70Å     R-factor:   0.180    
Authors: W.P.Burmeister,R.W.H.Ruigrok,S.Cusack
Key ref:
W.P.Burmeister et al. (1993). Influenza B virus neuraminidase can synthesize its own inhibitor. Structure, 1, 19-26. PubMed id: 8069621
Date:
24-May-93     Release date:   31-Oct-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P27907  (NRAM_INBBE) -  Neuraminidase
Seq:
Struc:
465 a.a.
390 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  

 

 
Structure 1:19-26 (1993)
PubMed id: 8069621  
 
 
Influenza B virus neuraminidase can synthesize its own inhibitor.
W.P.Burmeister, B.Henrissat, C.Bosso, S.Cusack, R.W.Ruigrok.
 
  ABSTRACT  
 
BACKGROUND: Neuraminidase, one of the two surface glycoproteins of influenza virus, cleaves terminal sialic acid residues from glycolipids or glycoproteins. Its crystal structure is known at high resolution, but the mechanism of glycosyl hydrolysis remains unclear. RESULTS: We have determined the crystal structure at 1.8 A resolution of two complexes of influenza B/Beijing neuraminidase containing either the reaction product, sialic acid, or the transition state analogue inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). The sialic acid is bound in a distorted 'boat' conformation closely resembling that of bound DANA, stabilized by a conserved tyrosine residue (Tyr408). This distortion also gives rise to a suicidal side reaction that converts sialic acid to DANA at a low rate. CONCLUSIONS: The mechanism of neuraminidase action is distinct from that of other known glycosyl hydrolases. Substrate distortion appears to be the driving force in glycosyl bond hydrolysis and the proton required for catalysis can probably be donated by water, rather than by residues in the active site, thus allowing the enzyme to operate at high pH. The side reaction converting sialic acid to DANA appears reasonably favourable, and it is unclear how this is minimized by the enzyme.
 

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.  
20364833 D.Paul, S.E.O'Leary, K.Rajashankar, W.Bu, A.Toms, E.C.Settembre, J.M.Sanders, T.P.Begley, and S.E.Ealick (2010).
Glycal formation in crystals of uridine phosphorylase.
  Biochemistry, 49, 3499-3509.
PDB codes: 3ku4 3kuk 3kvr 3kvv 3kvy
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.  
18941902 R.Gil-Redondo, J.Estrada, A.Morreale, F.Herranz, J.Sancho, and A.R.Ortiz (2009).
VSDMIP: virtual screening data management on an integrated platform.
  J Comput Aided Mol Des, 23, 171-184.  
18480754 P.J.Collins, L.F.Haire, Y.P.Lin, J.Liu, R.J.Russell, P.A.Walker, J.J.Skehel, S.R.Martin, A.J.Hay, and S.J.Gamblin (2008).
Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants.
  Nature, 453, 1258-1261.
PDB codes: 3ckz 3cl0 3cl2
18218621 S.L.Newstead, J.A.Potter, J.C.Wilson, G.Xu, C.H.Chien, A.G.Watts, S.G.Withers, and G.L.Taylor (2008).
The structure of Clostridium perfringens NanI sialidase and its catalytic intermediates.
  J Biol Chem, 283, 9080-9088.
PDB codes: 2bf6 2vk5 2vk6 2vk7
18049471 M.von Itzstein (2007).
The war against influenza: discovery and development of sialidase inhibitors.
  Nat Rev Drug Discov, 6, 967-974.  
16915235 R.J.Russell, L.F.Haire, D.J.Stevens, P.J.Collins, Y.P.Lin, G.M.Blackburn, A.J.Hay, S.J.Gamblin, and J.J.Skehel (2006).
The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design.
  Nature, 443, 45-49.
PDB codes: 2ht5 2ht7 2ht8 2htq 2htr 2htu 2htv 2htw 2hty 2hu0 2hu4
16206228 J.N.Watson, S.Newstead, A.A.Narine, G.Taylor, and A.J.Bennet (2005).
Two nucleophilic mutants of the Micromonospora viridifaciens sialidase operate with retention of configuration by two different mechanisms.
  Chembiochem, 6, 1999-2004.
PDB code: 1wcq
15501818 L.M.Chavas, C.Tringali, P.Fusi, B.Venerando, G.Tettamanti, R.Kato, E.Monti, and S.Wakatsuki (2005).
Crystal structure of the human cytosolic sialidase Neu2. Evidence for the dynamic nature of substrate recognition.
  J Biol Chem, 280, 469-475.
PDB codes: 1snt 1so7 1vcu
15893670 P.Yuan, T.B.Thompson, B.A.Wurzburg, R.G.Paterson, R.A.Lamb, and T.S.Jardetzky (2005).
Structural studies of the parainfluenza virus 5 hemagglutinin-neuraminidase tetramer in complex with its receptor, sialyllactose.
  Structure, 13, 803-815.
PDB codes: 1z4v 1z4w 1z4x 1z4y 1z4z 1z50
14634017 A.R.Todeschini, W.B.Dias, M.F.Girard, J.M.Wieruszeski, L.Mendonça-Previato, and J.O.Previato (2004).
Enzymatically inactive trans-sialidase from Trypanosoma cruzi binds sialyl and beta-galactopyranosyl residues in a sequential ordered mechanism.
  J Biol Chem, 279, 5323-5328.  
15226294 I.Moustafa, H.Connaris, M.Taylor, V.Zaitsev, J.C.Wilson, M.J.Kiefel, M.von Itzstein, and G.Taylor (2004).
Sialic acid recognition by Vibrio cholerae neuraminidase.
  J Biol Chem, 279, 40819-40826.
PDB codes: 1w0o 1w0p
15130470 M.F.Amaya, A.G.Watts, I.Damager, A.Wehenkel, T.Nguyen, A.Buschiazzo, G.Paris, A.C.Frasch, S.G.Withers, and P.M.Alzari (2004).
Structural insights into the catalytic mechanism of Trypanosoma cruzi trans-sialidase.
  Structure, 12, 775-784.
PDB codes: 1s0i 1s0j 1s0k 2ah2
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.  
15016893 V.Zaitsev, M.von Itzstein, D.Groves, M.Kiefel, T.Takimoto, A.Portner, and G.Taylor (2004).
Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: implications for fusion.
  J Virol, 78, 3733-3741.
PDB codes: 1usr 1usx
12974389 E.Tiralongo, I.Martensen, J.Grötzinger, J.Tiralongo, and R.Schauer (2003).
Trans-sialidase-like sequences from Trypanosoma congolense conserve most of the critical active site residues found in other trans-sialidases.
  Biol Chem, 384, 1203-1213.  
11994155 D.R.Leggate, J.M.Bryant, M.B.Redpath, D.Head, P.W.Taylor, and J.P.Luzio (2002).
Expression, mutagenesis and kinetic analysis of recombinant K1E endosialidase to define the site of proteolytic processing and requirements for catalysis.
  Mol Microbiol, 44, 749-760.  
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
11746676 H.Kamei, K.Shimazaki, and Y.Nishi (2001).
Computational 3-D modeling and site-directed mutation of an antibody that binds Neu2en5Ac, a transition state analogue of a sialic acid.
  Proteins, 45, 285-296.  
11239770 T.G.Morrison (2001).
The three faces of paramyxovirus attachment proteins.
  Trends Microbiol, 9, 103-105.  
11502530 W.M.Kati, D.Montgomery, C.Maring, V.S.Stoll, V.Giranda, X.Chen, W.G.Laver, W.Kohlbrenner, and D.W.Norbeck (2001).
Novel alpha- and beta-amino acid inhibitors of influenza virus neuraminidase.
  Antimicrob Agents Chemother, 45, 2563-2570.  
10619840 A.Buschiazzo, G.A.Tavares, O.Campetella, S.Spinelli, M.L.Cremona, G.París, M.F.Amaya, A.C.Frasch, and P.M.Alzari (2000).
Structural basis of sialyltransferase activity in trypanosomal sialidases.
  EMBO J, 19, 16-24.
PDB codes: 1mz5 1mz6
10801342 J.Yang, S.Schenkman, and B.A.Horenstein (2000).
Primary 13C and beta-secondary 2H KIEs for trans-sialidase. A snapshot of nucleophilic participation during catalysis.
  Biochemistry, 39, 5902-5910.  
10368285 J.N.Varghese, M.Hrmova, and G.B.Fincher (1999).
Three-dimensional structure of a barley beta-D-glucan exohydrolase, a family 3 glycosyl hydrolase.
  Structure, 7, 179-190.
PDB code: 1ex1
9753433 K.Gruber, G.Klintschar, M.Hayn, A.Schlacher, W.Steiner, and C.Kratky (1998).
Thermophilic xylanase from Thermomyces lanuginosus: high-resolution X-ray structure and modeling studies.
  Biochemistry, 37, 13475-13485.
PDB code: 1yna
9562562 Y.Luo, S.C.Li, M.Y.Chou, Y.T.Li, and M.Luo (1998).
The crystal structure of an intramolecular trans-sialidase with a NeuAc alpha2-->3Gal specificity.
  Structure, 6, 521-530.
PDB codes: 1sli 1sll
  9223510 J.P.Langedijk, F.J.Daus, and J.T.van Oirschot (1997).
Sequence and structure alignment of Paramyxoviridae attachment proteins and discovery of enzymatic activity for a morbillivirus hemagglutinin.
  J Virol, 71, 6155-6167.  
  9094607 L.V.Gubareva, M.J.Robinson, R.C.Bethell, and R.G.Webster (1997).
Catalytic and framework mutations in the neuraminidase active site of influenza viruses that are resistant to 4-guanidino-Neu5Ac2en.
  J Virol, 71, 3385-3390.  
8591030 A.Gaskell, S.Crennell, and G.Taylor (1995).
The three domains of a bacterial sialidase: a beta-propeller, an immunoglobulin module and a galactose-binding jelly-roll.
  Structure, 3, 1197-1205.
PDB codes: 1eur 1eus 1eut 1euu
8535779 G.Davies, and B.Henrissat (1995).
Structures and mechanisms of glycosyl hydrolases.
  Structure, 3, 853-859.  
7712292 J.D.McCarter, and S.G.Withers (1994).
Mechanisms of enzymatic glycoside hydrolysis.
  Curr Opin Struct Biol, 4, 885-892.  
  7849585 P.M.Colman (1994).
Influenza virus neuraminidase: structure, antibodies, and inhibitors.
  Protein Sci, 3, 1687-1696.  
7922030 S.Crennell, E.Garman, G.Laver, E.Vimr, and G.Taylor (1994).
Crystal structure of Vibrio cholerae neuraminidase reveals dual lectin-like domains in addition to the catalytic domain.
  Structure, 2, 535-544.
PDB code: 1kit
8234325 S.J.Crennell, E.F.Garman, W.G.Laver, E.R.Vimr, and G.L.Taylor (1993).
Crystal structure of a bacterial sialidase (from Salmonella typhimurium LT2) shows the same fold as an influenza virus neuraminidase.
  Proc Natl Acad Sci U S A, 90, 9852-9856.
PDB codes: 1sil 1sim
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.