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PDBsum entry 1nsb

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Hydrolase(o-glycosyl) PDB id
1nsb
Jmol
Contents
Protein chains
390 a.a.
Ligands
NAG ×2
Metals
_CA ×3
Waters ×1332
PDB id:
1nsb
Name: Hydrolase(o-glycosyl)
Title: The 2.2 angstroms resolution crystal structure of influenza neuraminidase and its complex with sialic acid
Structure: Neuraminidase. Chain: a, b. Engineered: yes
Source: Influenza b virus (strain b/beijing/1/ organism_taxid: 11525. Strain: b/beijing/1/87
Resolution:
2.20Å     R-factor:   0.148    
Authors: W.P.Burmeister,R.W.H.Ruigrok,S.Cusack
Key ref: W.P.Burmeister et al. (1992). The 2.2 A resolution crystal structure of influenza B neuraminidase and its complex with sialic acid. EMBO J, 11, 49-56. PubMed id: 1740114
Date:
08-Aug-91     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  

 

 
EMBO J 11:49-56 (1992)
PubMed id: 1740114  
 
 
The 2.2 A resolution crystal structure of influenza B neuraminidase and its complex with sialic acid.
W.P.Burmeister, R.W.Ruigrok, S.Cusack.
 
  ABSTRACT  
 
Influenza virus neuraminidase catalyses the cleavage of terminal sialic acid, the viral receptor, from carbohydrate chains on glycoproteins and glycolipids. We present the crystal structure of the enzymatically active head of influenza B virus neuraminidase from the strain B/Beijing/1/87. The native structure has been refined to a crystallographic R-factor of 14.8% at 2.2 A resolution and its complex with sialic acid refined at 2.8 A resolution. The overall fold of the molecule is very similar to the already known structure of neuraminidase from influenza A virus, with which there is amino acid sequence homology of approximately 30%. Two calcium binding sites have been identified. One of them, previously undescribed, is located between the active site and a large surface antigenic loop. The calcium ion is octahedrally co-ordinated by five oxygen atoms from the protein and one water molecule. Sequence comparisons suggest that this calcium site should occur in all influenza A and B virus neuraminidases. Soaking of sialic acid into the crystals has enabled the mode of binding of the reaction product in the putative active site pocket to be revealed. All the large side groups of the sialic acid are equatorial and are specifically recognized by nine fully conserved active site residues. These in turn are stabilized by a second shell of 10 highly conserved residues principally by an extensive network of hydrogen bonds.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21232128 J.R.Tisoncik, Y.Guo, K.S.Cordero, J.Yu, J.Wang, Y.Cao, and L.Rong (2011).
Identification of critical residues of influenza neuraminidase in viral particle release.
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21217702 T.Hashiguchi, T.Ose, M.Kubota, N.Maita, J.Kamishikiryo, K.Maenaka, and Y.Yanagi (2011).
Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM.
  Nat Struct Mol Biol, 18, 135-141.
PDB codes: 3alw 3alx 3alz
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
20124697 E.C.Schulz, P.Neumann, R.Gerardy-Schahn, G.M.Sheldrick, and R.Ficner (2010).
Structure analysis of endosialidase NF at 0.98 A resolution.
  Acta Crystallogr D Biol Crystallogr, 66, 176-180.
PDB code: 3ju4
20427563 E.E.Fry, T.J.Tuthill, K.Harlos, T.S.Walter, D.J.Rowlands, and D.I.Stuart (2010).
Crystal structure of equine rhinitis A virus in complex with its sialic acid receptor.
  J Gen Virol, 91, 1971-1977.
PDB code: 2xbo
20538598 S.J.Gamblin, and J.J.Skehel (2010).
Influenza hemagglutinin and neuraminidase membrane glycoproteins.
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19458903 J.Uhlendorff, T.Matrosovich, H.D.Klenk, and M.Matrosovich (2009).
Functional significance of the hemadsorption activity of influenza virus neuraminidase and its alteration in pandemic viruses.
  Arch Virol, 154, 945-957.  
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.
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19575039 Y.Nishimura (2009).
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18684820 N.M.Bouvier, A.C.Lowen, and P.Palese (2008).
Oseltamivir-resistant influenza A viruses are transmitted efficiently among guinea pigs by direct contact but not by aerosol.
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18715929 X.Xu, X.Zhu, R.A.Dwek, J.Stevens, and I.A.Wilson (2008).
Structural characterization of the 1918 influenza virus H1N1 neuraminidase.
  J Virol, 82, 10493-10501.
PDB codes: 3b7e 3beq
17426694 C.Y.Li, Q.Yu, Z.Q.Ye, Y.Sun, Q.He, X.M.Li, W.Zhang, J.Luo, X.Gu, X.Zheng, and L.Wei (2007).
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17616798 S.Perk, C.Banet-Noach, N.Golender, L.Simanov, E.Rozenblut, S.Nagar, S.Pokamunski, M.Pirak, Y.Tendler, M.García, and A.Panshin (2007).
Molecular characterization of the glycoprotein genes of H5N1 influenza A viruses isolated in Israel and the Gaza Strip during 2006 outbreaks.
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16641465 A.C.Hurt, P.Iannello, K.Jachno, N.Komadina, A.W.Hampson, I.G.Barr, and J.L.McKimm-Breschkin (2006).
Neuraminidase inhibitor-resistant and -sensitive influenza B viruses isolated from an untreated human patient.
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16702222 A.Müller, E.Severi, C.Mulligan, A.G.Watts, D.J.Kelly, K.S.Wilson, A.J.Wilkinson, and G.H.Thomas (2006).
Conservation of structure and mechanism in primary and secondary transporters exemplified by SiaP, a sialic acid binding virulence factor from Haemophilus influenzae.
  J Biol Chem, 281, 22212-22222.
PDB codes: 2cex 2cey
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.  
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
15892972 J.A.McCullers, E.Hoffmann, V.C.Huber, and A.D.Nickerson (2005).
A single amino acid change in the C-terminal domain of the matrix protein M1 of influenza B virus confers mouse adaptation and virulence.
  Virology, 336, 318-326.  
15608653 K.Stummeyer, A.Dickmanns, M.Mühlenhoff, R.Gerardy-Schahn, and R.Ficner (2005).
Crystal structure of the polysialic acid-degrading endosialidase of bacteriophage K1F.
  Nat Struct Mol Biol, 12, 90-96.
PDB codes: 1v0e 1v0f
16251290 V.P.Mishin, F.G.Hayden, and L.V.Gubareva (2005).
Susceptibilities of antiviral-resistant influenza viruses to novel neuraminidase inhibitors.
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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
14730352 C.P.Chiu, A.G.Watts, L.L.Lairson, M.Gilbert, D.Lim, W.W.Wakarchuk, S.G.Withers, and N.C.Strynadka (2004).
Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog.
  Nat Struct Mol Biol, 11, 163-170.
PDB codes: 1ro7 1ro8
14973124 F.Alberto, C.Bignon, G.Sulzenbacher, B.Henrissat, and M.Czjzek (2004).
The three-dimensional structure of invertase (beta-fructosidase) from Thermotoga maritima reveals a bimodular arrangement and an evolutionary relationship between retaining and inverting glycosidases.
  J Biol Chem, 279, 18903-18910.
PDB codes: 1utw 1uyp
15337401 M.Kiso, K.Mitamura, Y.Sakai-Tagawa, K.Shiraishi, C.Kawakami, K.Kimura, F.G.Hayden, N.Sugaya, and Y.Kawaoka (2004).
Resistant influenza A viruses in children treated with oseltamivir: descriptive study.
  Lancet, 364, 759-765.  
12785732 C.H.Lee, S.I.Kim, K.B.Lee, Y.C.Yoo, S.Y.Ryu, and K.S.Song (2003).
Neuraminidase inhibitors from Reynoutria elliptica.
  Arch Pharm Res, 26, 367-374.  
14580216 J.N.Watson, V.Dookhun, T.J.Borgford, and A.J.Bennet (2003).
Mutagenesis of the conserved active-site tyrosine changes a retaining sialidase into an inverting sialidase.
  Biochemistry, 42, 12682-12690.  
12574276 N.T.Wetherall, T.Trivedi, J.Zeller, C.Hodges-Savola, J.L.McKimm-Breschkin, M.Zambon, and F.G.Hayden (2003).
Evaluation of neuraminidase enzyme assays using different substrates to measure susceptibility of influenza virus clinical isolates to neuraminidase inhibitors: report of the neuraminidase inhibitor susceptibility network.
  J Clin Microbiol, 41, 742-750.  
11897581 C.Sweet, K.J.Jakeman, K.Bush, P.C.Wagaman, L.A.McKown, A.J.Streeter, D.Desai-Krieger, P.Chand, and Y.S.Babu (2002).
Oral administration of cyclopentane neuraminidase inhibitors protects ferrets against influenza virus infection.
  Antimicrob Agents Chemother, 46, 996.  
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.  
11829724 J.L.McKimm-Breschkin (2002).
Neuraminidase inhibitors for the treatment and prevention of influenza.
  Expert Opin Pharmacother, 3, 103-112.  
12435681 M.Z.Wang, C.Y.Tai, and D.B.Mendel (2002).
Mechanism by which mutations at his274 alter sensitivity of influenza a virus n1 neuraminidase to oseltamivir carboxylate and zanamivir.
  Antimicrob Agents Chemother, 46, 3809-3816.  
11779391 D.Young, C.Fowler, and K.Bush (2001).
RWJ-270201 (BCX-1812): a novel neuraminidase inhibitor for influenza.
  Philos Trans R Soc Lond B Biol Sci, 356, 1905-1913.  
11381099 M.J.Jedrzejas (2001).
Pneumococcal virulence factors: structure and function.
  Microbiol Mol Biol Rev, 65, 187.  
11413297 M.T.Murrell, M.Porotto, O.Greengard, N.Poltoratskaia, and A.Moscona (2001).
A single amino acid alteration in the human parainfluenza virus type 3 hemagglutinin-neuraminidase glycoprotein confers resistance to the inhibitory effects of zanamivir on receptor binding and neuraminidase activity.
  J Virol, 75, 6310-6320.  
11298736 Y.Wang, K.Yamaguchi, Y.Shimada, X.Zhao, and T.Miyagi (2001).
Site-directed mutagenesis of human membrane-associated ganglioside sialidase: identification of amino-acid residues contributing to substrate specificity.
  Eur J Biochem, 268, 2201-2208.  
10692451 J.J.Pitt, E.Da Silva, and J.J.Gorman (2000).
Determination of the disulfide bond arrangement of Newcastle disease virus hemagglutinin neuraminidase. Correlation with a beta-sheet propeller structural fold predicted for paramyxoviridae attachment proteins.
  J Biol Chem, 275, 6469-6478.  
  10400772 D.Kobasa, S.Kodihalli, M.Luo, M.R.Castrucci, I.Donatelli, Y.Suzuki, T.Suzuki, and Y.Kawaoka (1999).
Amino acid residues contributing to the substrate specificity of the influenza A virus neuraminidase.
  J Virol, 73, 6743-6751.  
10997129 L.Jindrák, and L.Grubhoffer (1999).
Animal virus receptors.
  Folia Microbiol (Praha), 44, 467-486.  
11504496 P.R.Wyde (1999).
Chemotherapy of respiratory viruses: prospects and challenges.
  Drug Resist Updat, 2, 244-258.  
10440735 W.A.Grow, M.Ferns, and H.Gordon (1999).
Agrin-independent activation of the agrin signal transduction pathway.
  J Neurobiol, 40, 356-365.  
9501080 A.van der Spoel, E.Bonten, and A.d'Azzo (1998).
Transport of human lysosomal neuraminidase to mature lysosomes requires protective protein/cathepsin A.
  EMBO J, 17, 1588-1597.  
15991949 C.Cianci, and M.Krystal (1998).
Development of antivirals against influenza.
  Expert Opin Investig Drugs, 7, 149-165.  
  9835519 C.Y.Tai, P.A.Escarpe, R.W.Sidwell, M.A.Williams, W.Lew, H.Wu, C.U.Kim, and D.B.Mendel (1998).
Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS 4071.
  Antimicrob Agents Chemother, 42, 3234-3241.  
  9517945 D.B.Mendel, C.Y.Tai, P.A.Escarpe, W.Li, R.W.Sidwell, J.H.Huffman, C.Sweet, K.J.Jakeman, J.Merson, S.A.Lacy, W.Lew, M.A.Williams, L.Zhang, M.S.Chen, N.Bischofberger, and C.U.Kim (1998).
Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infection.
  Antimicrob Agents Chemother, 42, 640-646.  
17092804 D.B.Mendel, and R.W.Sidwell (1998).
Influenza virus resistance to neuraminidase inhibitors.
  Drug Resist Updat, 1, 184-189.  
9707628 H.Goto, and Y.Kawaoka (1998).
A novel mechanism for the acquisition of virulence by a human influenza A virus.
  Proc Natl Acad Sci U S A, 95, 10224-10228.  
  9521098 S.Jones, M.Stewart, A.Michie, M.B.Swindells, C.Orengo, and J.M.Thornton (1998).
Domain assignment for protein structures using a consensus approach: characterization and analysis.
  Protein Sci, 7, 233-242.  
9342319 J.N.Varghese, P.M.Colman, A.van Donkelaar, T.J.Blick, A.Sahasrabudhe, and J.L.McKimm-Breschkin (1997).
Structural evidence for a second sialic acid binding site in avian influenza virus neuraminidases.
  Proc Natl Acad Sci U S A, 94, 11808-11812.
PDB code: 1mwe
9331424 R.C.Wade (1997).
'Flu' and structure-based drug design.
  Structure, 5, 1139-1145.  
  9032355 R.Gajardo, P.Vende, D.Poncet, and J.Cohen (1997).
Two proline residues are essential in the calcium-binding activity of rotavirus VP7 outer capsid protein.
  J Virol, 71, 2211-2216.  
8990162 T.A.Springer (1997).
Folding of the N-terminal, ligand-binding region of integrin alpha-subunits into a beta-propeller domain.
  Proc Natl Acad Sci U S A, 94, 65-72.  
  8787876 J.L.McKimm-Breschkin, T.J.Blick, A.Sahasrabudhe, T.Tiong, D.Marshall, G.J.Hart, R.C.Bethell, and C.R.Penn (1996).
Generation and characterization of variants of NWS/G70C influenza virus after in vitro passage in 4-amino-Neu5Ac2en and 4-guanidino-Neu5Ac2en.
  Antimicrob Agents Chemother, 40, 40-46.  
8581891 M.Murakami, K.Ikeda, and K.Achiwa (1996).
Chemoenzymatic synthesis of neuraminic acid analogs structurally varied at C-5 and C-9 as potential inhibitors of the sialidase from influenza virus.
  Carbohydr Res, 280, 101-110.  
8736551 U.Skoging, M.Vihinen, L.Nilsson, and P.Liljeström (1996).
Aromatic interactions define the binding of the alphavirus spike to its nucleocapsid.
  Structure, 4, 519-529.  
8634279 V.Helms, E.Deprez, E.Gill, C.Barret, G.Hui Bon Hoa, and R.C.Wade (1996).
Improved binding of cytochrome P450cam substrate analogues designed to fill extra space in the substrate binding pocket.
  Biochemistry, 35, 1485-1499.  
8879557 W.Fitz, P.B.Rosenthal, and C.H.Wong (1996).
Synthesis and inhibitory properties of a thiomethylmercuric sialic acid with application to the X-ray structure determination of 9-O-acetylsialic acid esterase from influenza C virus.
  Bioorg Med Chem, 4, 1349-1353.  
8710874 Z.Y.Zhu, and S.Karlin (1996).
Clusters of charged residues in protein three-dimensional structures.
  Proc Natl Acad Sci U S A, 93, 8350-8355.  
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
  7549872 J.N.Varghese, V.C.Epa, and P.M.Colman (1995).
Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase.
  Protein Sci, 4, 1081-1087.
PDB codes: 1nnc 7nn9
8592707 M.J.Jedrzejas, S.Singh, W.J.Brouillette, G.M.Air, and M.Luo (1995).
A strategy for theoretical binding constant, Ki, calculations for neuraminidase aromatic inhibitors designed on the basis of the active site structure of influenza virus neuraminidase.
  Proteins, 23, 264-277.
PDB code: 1ing
  8035509 A.M.Mirza, R.Deng, and R.M.Iorio (1994).
Site-directed mutagenesis of a conserved hexapeptide in the paramyxovirus hemagglutinin-neuraminidase glycoprotein: effects on antigenic structure and function.
  J Virol, 68, 5093-5099.  
8134399 B.E.Johansson, and E.D.Kilbourne (1994).
Immunization with purified N1 and N2 influenza virus neuraminidases demonstrates cross-reactivity without antigenic competition.
  Proc Natl Acad Sci U S A, 91, 2358-2361.  
  8289360 F.Yamamoto-Goshima, K.Maeno, T.Morishita, M.Ueda, Y.Fujita, K.Nakajima, and S.Yoshii (1994).
Role of neuraminidase in the morphogenesis of influenza B virus.
  J Virol, 68, 1250-1254.  
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.  
  7509002 T.Saito, G.Taylor, W.G.Laver, Y.Kawaoka, and R.G.Webster (1994).
Antigenicity of the N8 influenza A virus neuraminidase: existence of an epitope at the subunit interface of the neuraminidase.
  J Virol, 68, 1790-1796.  
7870741 Y.Suzuki (1994).
Gangliosides as influenza virus receptors. Variation of influenza viruses and their recognition of the receptor sialo-sugar chains.
  Prog Lipid Res, 33, 429-457.  
  8251933 A.W.Chan, E.G.Hutchinson, D.Harris, and J.M.Thornton (1993).
Identification, classification, and analysis of beta-bulges in proteins.
  Protein Sci, 2, 1574-1590.  
7680132 J.M.Nuss, P.B.Whitaker, and G.M.Air (1993).
Identification of critical contact residues in the NC41 epitope of a subtype N9 influenza virus neuraminidase.
  Proteins, 15, 121-132.  
  8497041 P.M.Colman, P.A.Hoyne, and M.C.Lawrence (1993).
Sequence and structure alignment of paramyxovirus hemagglutinin-neuraminidase with influenza virus neuraminidase.
  J Virol, 67, 2972-2980.  
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
  8411368 S.Li, J.Schulman, S.Itamura, and P.Palese (1993).
Glycosylation of neuraminidase determines the neurovirulence of influenza A/WSN/33 virus.
  J Virol, 67, 6667-6673.  
  8497050 S.Shibata, F.Yamamoto-Goshima, K.Maeno, T.Hanaichi, Y.Fujita, K.Nakajima, M.Imai, T.Komatsu, and S.Sugiura (1993).
Characterization of a temperature-sensitive influenza B virus mutant defective in neuraminidase.
  J Virol, 67, 3264-3273.  
8069621 W.P.Burmeister, B.Henrissat, C.Bosso, S.Cusack, and R.W.Ruigrok (1993).
Influenza B virus neuraminidase can synthesize its own inhibitor.
  Structure, 1, 19-26.
PDB codes: 1nsc 1nsd
1490102 T.Roggentin, R.G.Kleineidam, R.Schauer, and P.Roggentin (1992).
Effects of site-specific mutations on the enzymatic properties of a sialidase from Clostridium perfringens.
  Glycoconj J, 9, 235-240.  
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.