PDBsum entry 1euu

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Hydrolase PDB id
Jmol PyMol
Protein chain
601 a.a. *
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Sialidase or neuraminidase, large 68kd form
Structure: Sialidase. Chain: a. Synonym: neuraminidase. Other_details: large 68kd form
Source: Micromonospora viridifaciens. Organism_taxid: 1881. Atcc: 31146
2.50Å     R-factor:   0.228    
Authors: A.Gaskell,S.J.Crennell,G.L.Taylor
Key ref:
A.Gaskell et al. (1995). The three domains of a bacterial sialidase: a beta-propeller, an immunoglobulin module and a galactose-binding jelly-roll. Structure, 3, 1197-1205. PubMed id: 8591030 DOI: 10.1016/S0969-2126(01)00255-6
21-Jun-96     Release date:   11-Jan-97    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q02834  (NANH_MICVI) -  Sialidase
647 a.a.
601 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 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     extracellular region   1 term 
  Biological process     metabolic process   1 term 
  Biochemical function     exo-alpha-(2->3)-sialidase activity     6 terms  


DOI no: 10.1016/S0969-2126(01)00255-6 Structure 3:1197-1205 (1995)
PubMed id: 8591030  
The three domains of a bacterial sialidase: a beta-propeller, an immunoglobulin module and a galactose-binding jelly-roll.
A.Gaskell, S.Crennell, G.Taylor.
BACKGROUND: Sialidases, or neuraminidases, have been implicated in the pathogenesis of many diseases, but are also produced by many non-pathogenic bacteria. Bacterial sialidases are very variable in size, often possessing domains in addition to the catalytic domain. The sialidase from the non-pathogenic soil bacterium Micromonospora viridifaciens is secreted in two forms with molecular weights of 41 kDa or 68 kDa, depending on the nature of the carbohydrate used to induce expression. RESULTS: We report here the X-ray crystal structures of the 41 kDa and 68 kDa forms of the sialidase from M. viridifaciens at 1.8 A and 2.5 A resolution respectively. In addition, we report a complex of the 41 kDa form with an inhibitor at 2.0 A resolution, and a complex of the 68 kDa form with galactose at 2.5 A. The 41 kDa form shows the canonical sialidase beta-propeller fold. The 68 kDa form possesses two additional domains, one with an immunoglobulin-like fold that serves as a linker to the second, which is homologous to the galactose-binding domain of a fungal galactose oxidase. CONCLUSIONS: The presence of the additional carbohydrate-binding domain in the 68 kDa form of the bacterial sialidase reported here is a further example of a combination of carbohydrate binding and cleaving domains which we observed in the sialidase from Vibrio cholerae. This dual function may be common, but only to other bacterial and parasitic sialidases, but also to other secreted glycosidases involved in pathogenesis. The bacterium may have acquired both the immunoglobulin module and the galactose-binding module from eukaryotes, as the enzyme shows a remarkable similarity to a fungal galactose oxidase which possesses similar domains performing different functions and assembled in a different order.
  Selected figure(s)  
Figure 4.
Figure 4. Stereoview Cα traces of the additional domains in the 68 kDa form of the enzyme. (a) The immunoglobulin-like linker domain (residues 403–505). (b) The galactose-binding domain (residues 506–647). Figure 4. Stereoview Cα traces of the additional domains in the 68 kDa form of the enzyme. (a) The immunoglobulin-like linker domain (residues 403–505). (b) The galactose-binding domain (residues 506–647).
Figure 5.
Figure 5. Stereoview of the 2.5 å difference Fourier electron-density map showing the binding of galactose and its environment in the 68 kDa form of M. viridifaciens sialidase. Map contoured at 3σ. Figure 5. Stereoview of the 2.5 å difference Fourier electron-density map showing the binding of galactose and its environment in the 68 kDa form of M. viridifaciens sialidase. Map contoured at 3σ.
  The above figures are reprinted by permission from Cell Press: Structure (1995, 3, 1197-1205) copyright 1995.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21307569 M.Kitami, T.Kadotani, K.Nakanishi, S.Atsumi, S.Higurashi, T.Ishizaka, A.Watanabe, and R.Sato (2011).
Bacillus thuringiensis Cry toxins bound specifically to various proteins via domain III, which had a galactose-binding domain-like fold.
  Biosci Biotechnol Biochem, 75, 305-312.  
21240549 T.Lieke, D.Gröbe, V.Blanchard, D.Grunow, R.Tauber, M.Zimmermann-Kordmann, T.Jacobs, and W.Reutter (2011).
Invasion of Trypanosoma cruzi into host cells is impaired by N-propionylmannosamine and other N-acylmannosamines.
  Glycoconj J, 28, 31-37.  
  20944224 A.P.Yeh, P.Abdubek, T.Astakhova, H.L.Axelrod, C.Bakolitsa, X.Cai, D.Carlton, C.Chen, H.J.Chiu, M.Chiu, T.Clayton, D.Das, M.C.Deller, L.Duan, K.Ellrott, C.L.Farr, J.Feuerhelm, J.C.Grant, A.Grzechnik, G.W.Han, L.Jaroszewski, K.K.Jin, H.E.Klock, M.W.Knuth, P.Kozbial, S.S.Krishna, A.Kumar, W.W.Lam, D.Marciano, D.McMullan, M.D.Miller, A.T.Morse, E.Nigoghossian, A.Nopakun, L.Okach, C.Puckett, R.Reyes, H.J.Tien, C.B.Trame, H.van den Bedem, D.Weekes, T.Wooten, Q.Xu, K.O.Hodgson, J.Wooley, M.A.Elsliger, A.M.Deacon, A.Godzik, S.A.Lesley, and I.A.Wilson (2010).
Structure of Bacteroides thetaiotaomicron BT2081 at 2.05 Å resolution: the first structural representative of a new protein family that may play a role in carbohydrate metabolism.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 66, 1287-1296.
PDB code: 3hbz
20939100 S.Kalkhof, S.Haehn, M.Paulsson, N.Smyth, J.Meiler, and A.Sinz (2010).
Computational modeling of laminin N-terminal domains using sparse distance constraints from disulfide bonds and chemical cross-linking.
  Proteins, 78, 3409-3427.  
19364485 D.Wang, S.Zaitsev, G.Taylor, A.d'Azzo, and E.Bonten (2009).
Protective Protein/Cathepsin A Rescues N-glycosylation defects in Neuraminidase-1.
  Biochim Biophys Acta, (), 0.  
19714866 D.Wang, S.Zaitsev, G.Taylor, A.d'Azzo, and E.Bonten (2009).
Protective protein/cathepsin A rescues N-glycosylation defects in neuraminidase-1.
  Biochim Biophys Acta, 1790, 275-282.  
19666471 E.J.Bonten, Y.Campos, V.Zaitsev, A.Nourse, B.Waddell, W.Lewis, G.Taylor, and A.d'Azzo (2009).
Heterodimerization of the sialidase NEU1 with the chaperone protective protein/cathepsin A prevents its premature oligomerization.
  J Biol Chem, 284, 28430-28441.  
19594936 E.M.Quistgaard, and S.S.Thirup (2009).
Sequence and structural analysis of the Asp-box motif and Asp-box beta-propellers; a widespread propeller-type characteristic of the Vps10 domain family and several glycoside hydrolase families.
  BMC Struct Biol, 9, 46.  
19269961 R.Carapito, A.Imberty, J.M.Jeltsch, S.C.Byrns, P.H.Tam, T.L.Lowary, A.Varrot, and V.Phalip (2009).
Molecular Basis of Arabinobio-hydrolase Activity in Phytopathogenic Fungi: CRYSTAL STRUCTURE AND CATALYTIC MECHANISM OF FUSARIUM GRAMINEARUM GH93 EXO-{alpha}-L-ARABINANASE.
  J Biol Chem, 284, 12285-12296.
PDB codes: 2w5n 2w5o
18816799 T.A.Ramelot, S.Raman, A.P.Kuzin, R.Xiao, L.C.Ma, T.B.Acton, J.F.Hunt, G.T.Montelione, D.Baker, and M.A.Kennedy (2009).
Improving NMR protein structure quality by Rosetta refinement: a molecular replacement study.
  Proteins, 75, 147-167.
PDB codes: 1tvg 1xpw
19930717 Y.M.Cheng, F.C.Hsieh, and M.Meng (2009).
Functional analysis of conserved aromatic amino acids in the discoidin domain of Paenibacillus beta-1,3-glucanase.
  Microb Cell Fact, 8, 62.  
  18772331 A.Hinek, T.D.Bodnaruk, S.Bunda, Y.Wang, and K.Liu (2008).
Neuraminidase-1, a subunit of the cell surface elastin receptor, desialylates and functionally inactivates adjacent receptors interacting with the mitogenic growth factors PDGF-BB and IGF-2.
  Am J Pathol, 173, 1042-1056.  
18384150 K.S.Aragão, M.Satre, A.Imberty, and A.Varrot (2008).
Structure determination of Discoidin II from Dictyostelium discoideum and carbohydrate binding properties of the lectin domain.
  Proteins, 73, 43-52.
PDB codes: 2vm9 2vmc 2vmd 2vme
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
17989695 B.A.Appleton, P.Wu, J.Maloney, J.Yin, W.C.Liang, S.Stawicki, K.Mortara, K.K.Bowman, J.M.Elliott, W.Desmarais, J.F.Bazan, A.Bagri, M.Tessier-Lavigne, A.W.Koch, Y.Wu, R.J.Watts, and C.Wiesmann (2007).
Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding.
  EMBO J, 26, 4902-4912.
PDB codes: 2qqi 2qqj 2qqk 2qql 2qqm 2qqn 2qqo
17703188 O.Ichikawa, M.Osawa, N.Nishida, N.Goshima, N.Nomura, and I.Shimada (2007).
Structural basis of the collagen-binding mode of discoidin domain receptor 2.
  EMBO J, 26, 4168-4176.
PDB code: 2z4f
17684740 T.K.Goulas, A.K.Goulas, G.Tzortzis, and G.R.Gibson (2007).
Molecular cloning and comparative analysis of four beta-galactosidase genes from Bifidobacterium bifidum NCIMB41171.
  Appl Microbiol Biotechnol, 76, 1365-1372.  
16990278 E.Ficko-Blean, and A.B.Boraston (2006).
The interaction of a carbohydrate-binding module from a Clostridium perfringens N-acetyl-beta-hexosaminidase with its carbohydrate receptor.
  J Biol Chem, 281, 37748-37757.
PDB codes: 2j1a 2j1e 2j7m
16575518 E.Villar, and I.M.Barroso (2006).
Role of sialic acid-containing molecules in paramyxovirus entry into the host cell: a minireview.
  Glycoconj J, 23, 5.  
16251191 E.W.Odom, and G.R.Vasta (2006).
Characterization of a binary tandem domain F-type lectin from striped bass (Morone saxatilis).
  J Biol Chem, 281, 1698-1713.  
16896351 J.M.Peters (2006).
The anaphase promoting complex/cyclosome: a machine designed to destroy.
  Nat Rev Mol Cell Biol, 7, 644-656.  
16569867 M.P.Malakhov, L.M.Aschenbrenner, D.F.Smee, M.K.Wandersee, R.W.Sidwell, L.V.Gubareva, V.P.Mishin, F.G.Hayden, D.H.Kim, A.Ing, E.R.Campbell, M.Yu, and F.Fang (2006).
Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection.
  Antimicrob Agents Chemother, 50, 1470-1479.  
17005007 M.S.Centeno, A.Goyal, J.A.Prates, L.M.Ferreira, H.J.Gilbert, and C.M.Fontes (2006).
Novel modular enzymes encoded by a cellulase gene cluster in Cellvibrio mixtus.
  FEMS Microbiol Lett, 265, 26-34.  
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
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
16239725 S.L.Newstead, J.N.Watson, A.J.Bennet, and G.Taylor (2005).
Galactose recognition by the carbohydrate-binding module of a bacterial sialidase.
  Acta Crystallogr D Biol Crystallogr, 61, 1483-1491.
PDB code: 2bzd
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 code: 1uyp
15678758 F.J.Stevens (2004).
Amyloid formation: an emulation of matrix protein assembly?
  Amyloid, 11, 232-244.  
15465324 G.R.Vasta, H.Ahmed, and E.W.Odom (2004).
Structural and functional diversity of lectin repertoires in invertebrates, protochordates and ectothermic vertebrates.
  Curr Opin Struct Biol, 14, 617-630.  
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
14997539 M.S.Sujatha, and P.V.Balaji (2004).
Identification of common structural features of binding sites in galactose-specific proteins.
  Proteins, 55, 44-65.  
15020593 N.Leulliot, S.Quevillon-Cheruel, I.Sorel, M.Graille, P.Meyer, D.Liger, K.Blondeau, J.Janin, and H.van Tilbeurgh (2004).
Crystal structure of yeast allantoicase reveals a repeated jelly roll motif.
  J Biol Chem, 279, 23447-23452.
PDB code: 1sg3
15229895 Q.Xu, R.Schwarzenbacher, R.Page, E.Sims, P.Abdubek, E.Ambing, T.Biorac, L.S.Brinen, J.Cambell, J.M.Canaves, H.J.Chiu, X.Dai, A.M.Deacon, M.DiDonato, M.A.Elsliger, R.Floyd, A.Godzik, C.Grittini, S.K.Grzechnik, E.Hampton, L.Jaroszewski, C.Karlak, H.E.Klock, E.Koesema, J.S.Kovarik, A.Kreusch, P.Kuhn, S.A.Lesley, I.Levin, D.McMullan, T.M.McPhillips, M.D.Miller, A.Morse, K.Moy, J.Ouyang, K.Quijano, R.Reyes, F.Rezezadeh, A.Robb, G.Spraggon, R.C.Stevens, H.van den Bedem, J.Velasquez, J.Vincent, F.von Delft, X.Wang, B.West, G.Wolf, K.O.Hodgson, J.Wooley, and I.A.Wilson (2004).
Crystal structure of an allantoicase (YIR029W) from Saccharomyces cerevisiae at 2.4 A resolution.
  Proteins, 56, 619-624.
PDB code: 1o59
15502328 S.Newstead, C.H.Chien, M.Taylor, and G.Taylor (2004).
Crystallization and atomic resolution X-ray diffraction of the catalytic domain of the large sialidase, nanI, from Clostridium perfringens.
  Acta Crystallogr D Biol Crystallogr, 60, 2063-2066.  
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.  
12732625 M.Wimmerova, E.Mitchell, J.F.Sanchez, C.Gautier, and A.Imberty (2003).
Crystal structure of fungal lectin: six-bladed beta-propeller fold and novel fucose recognition mode for Aleuria aurantia lectin.
  J Biol Chem, 278, 27059-27067.
PDB code: 1ofz
14517945 V.Seyrantepe, H.Poupetova, R.Froissart, M.T.Zabot, I.Maire, and A.V.Pshezhetsky (2003).
Molecular pathology of NEU1 gene in sialidosis.
  Hum Mutat, 22, 343-352.  
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.  
12071958 G.Montagna, M.L.Cremona, G.Paris, M.F.Amaya, A.Buschiazzo, P.M.Alzari, and A.C.Frasch (2002).
The trans-sialidase from the african trypanosome Trypanosoma brucei.
  Eur J Biochem, 269, 2941-2950.  
11799177 H.Connaris, T.Takimoto, R.Russell, S.Crennell, I.Moustafa, A.Portner, and G.Taylor (2002).
Probing the sialic acid binding site of the hemagglutinin-neuraminidase of Newcastle disease virus: identification of key amino acids involved in cell binding, catalysis, and fusion.
  J Virol, 76, 1816-1824.  
12091873 M.A.Bianchet, E.W.Odom, G.R.Vasta, and L.M.Amzel (2002).
A novel fucose recognition fold involved in innate immunity.
  Nat Struct Biol, 9, 628-634.
PDB code: 1k12
11401983 B.H.Jost, J.G.Songer, and S.J.Billington (2001).
Cloning, expression, and characterization of a neuraminidase gene from Arcanobacterium pyogenes.
  Infect Immun, 69, 4430-4437.  
11331068 J.Sondek, and D.P.Siderovski (2001).
Ggamma-like (GGL) domains: new frontiers in G-protein signaling and beta-propeller scaffolding.
  Biochem Pharmacol, 61, 1329-1337.  
11524682 K.S.Wendt, H.C.Vodermaier, U.Jacob, C.Gieffers, M.Gmachl, J.M.Peters, R.Huber, and P.Sondermann (2001).
Crystal structure of the APC10/DOC1 subunit of the human anaphase-promoting complex.
  Nat Struct Biol, 8, 784-788.
PDB code: 1jhj
11319112 P.L.Møller, F.Jørgensen, O.C.Hansen, S.M.Madsen, and P.Stougaard (2001).
Intra- and extracellular beta-galactosidases from Bifidobacterium bifidum and B. infantis: molecular cloning, heterologous expression, and comparative characterization.
  Appl Environ Microbiol, 67, 2276-2283.  
11308029 R.G.Kleineidam, S.Kruse, P.Roggentin, and R.Schauer (2001).
Elucidation of the role of functional amino acid residues of the small sialidase from Clostridium perfringens by site-directed mutagenesis.
  Biol Chem, 382, 313-319.  
10673426 S.Carr, C.N.Penfold, V.Bamford, R.James, and A.M.Hemmings (2000).
The structure of TolB, an essential component of the tol-dependent translocation system, and its protein-protein interaction with the translocation domain of colicin E9.
  Structure, 8, 57-66.
PDB code: 1c5k
11092845 S.Mizan, A.Henk, A.Stallings, M.Maier, and M.D.Lee (2000).
Cloning and characterization of sialidases with 2-6' and 2-3' sialyl lactose specificity from Pasteurella multocida.
  J Bacteriol, 182, 6874-6883.  
  10210191 D.H.Juers, R.E.Huber, and B.W.Matthews (1999).
Structural comparisons of TIM barrel proteins suggest functional and evolutionary relationships between beta-galactosidase and other glycohydrolases.
  Protein Sci, 8, 122-136.  
9585530 J.Stöckel, J.Safar, A.C.Wallace, F.E.Cohen, and S.B.Prusiner (1998).
Prion protein selectively binds copper(II) ions.
  Biochemistry, 37, 7185-7193.  
9761828 Y.Luo, M.Chou, S.Li, Y.Li, and M.Luo (1998).
Crystallization and preliminary X-ray studies of sialidase L from the leech Macrobdella decora.
  Acta Crystallogr D Biol Crystallogr, 54, 111-113.  
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
9365983 V.C.Epa (1997).
Modeling the paramyxovirus hemagglutinin-neuraminidase protein.
  Proteins, 29, 264-281.  
  8880921 A.Bateman, S.R.Eddy, and C.Chothia (1996).
Members of the immunoglobulin superfamily in bacteria.
  Protein Sci, 5, 1939-1941.  
8994884 G.Taylor (1996).
Sialidases: structures, biological significance and therapeutic potential.
  Curr Opin Struct Biol, 6, 830-837.  
8913694 M.von Itzstein, and P.Colman (1996).
Design and synthesis of carbohydrate-based inhibitors of protein-carbohydrate interactions.
  Curr Opin Struct Biol, 6, 703-709.  
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 code is shown on the right.