T00208
type: Enzyme
rlcp: p99
cath: Jelly Rolls
cath: Neuraminidase
ec: https://purl.uniprot.org/enzyme/3.2.1.18
uniprot: P0C6E9
kegg enzyme: exo-alpha-sialidase
kegg enzyme: neuraminidase
kegg enzyme: sialidase
kegg enzyme: alpha-neuraminidase
kegg enzyme: acetylneuraminidase
kegg pathway: N-Glycan degradation
kegg pathway: Sphingolipid metabolism
kegg pathway: Glycan structures - degradation
kegg cofactor: Calcium
kegg substrate: GT1b
kegg substrate: H2O
kegg substrate: GM3
kegg substrate: N-Acetylneuraminyl-galactosylceramide
kegg substrate: N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
kegg substrate: N-Acetylneuraminyl-D-galactosyl-N-acetyl-D-galactosaminyl-(N- acetylneuraminyl)-D-galactosyl-D-glucosylceramide
kegg substrate: GQ1
kegg product: N-Acetylneuraminate
kegg product: beta-D-Galactosyl-1,4-beta-D-glucosylceramide
kegg product: Galactosylceramide
kegg product: GA2
kegg product: D-Galactosyl-N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
kegg product: GT1b
kegg product: GD1b
pdb: 1kitA01
pdb: 1w0oA01
pdb: 1w0pA01
pdb: 1kitA02
pdb: 1w0oA02
pdb: 1w0pA02
pdb: 1kitA03
pdb: 1w0oA03
pdb: 1w0pA03
pdb bound state: Unbound
  compound: GM3
  pdb: 1kitA01
pdb bound state: Unbound
  compound: GM3
  pdb: 1w0oA01
pdb bound state: Unbound
  compound: GM3
  pdb: 1w0pA01
pdb bound state: Unbound
  compound: GM3
  pdb: 1kitA02
pdb bound state: Unbound
  compound: GM3
  pdb: 1w0oA02
pdb bound state: Unbound
  compound: GM3
  pdb: 1w0pA02
pdb bound state: Unbound
  compound: GM3
  pdb: 1kitA03
pdb bound state: Unbound
  compound: GM3
  pdb: 1w0oA03
pdb bound state: Unbound
  compound: GM3
  pdb: 1w0pA03
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-galactosylceramide
  pdb: 1kitA01
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-galactosylceramide
  pdb: 1w0oA01
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-galactosylceramide
  pdb: 1w0pA01
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-galactosylceramide
  pdb: 1kitA02
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-galactosylceramide
  pdb: 1w0oA02
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-galactosylceramide
  pdb: 1w0pA02
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-galactosylceramide
  pdb: 1kitA03
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-galactosylceramide
  pdb: 1w0oA03
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-galactosylceramide
  pdb: 1w0pA03
pdb bound state: Unbound
  compound: N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1kitA01
pdb bound state: Unbound
  compound: N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1w0oA01
pdb bound state: Unbound
  compound: N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1w0pA01
pdb bound state: Unbound
  compound: N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1kitA02
pdb bound state: Unbound
  compound: N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1w0oA02
pdb bound state: Unbound
  compound: N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1w0pA02
pdb bound state: Unbound
  compound: N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1kitA03
pdb bound state: Unbound
  compound: N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1w0oA03
pdb bound state: Unbound
  compound: N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1w0pA03
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-D-galactosyl-N-acetyl-D-galactosaminyl-(N- acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1kitA01
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-D-galactosyl-N-acetyl-D-galactosaminyl-(N- acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1w0oA01
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-D-galactosyl-N-acetyl-D-galactosaminyl-(N- acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1w0pA01
pdb bound state: Unbound
  compound: N-Acetylneuraminyl-D-galactosyl-N-acetyl-D-galactosaminyl-(N- acetylneuraminyl)-D-galactosyl-D-glucosylceramide
  pdb: 1kitA02
references: 2,3-Didehydro-2-deoxysialic acids structurally varied at C-5 and their behaviour towards the sialidase from Vibrio cholerae.
references: Purification, crystallization and preliminary crystallographic study of neuraminidase from Vibrio cholerae and Salmonella typhimurium LT2.
references: A kinetic-isotope-effect study of catalysis by Vibrio cholerae neuraminidase.
references: Crystal structure of Vibrio cholerae neuraminidase reveals dual lectin-like domains in addition to the catalytic domain.
references: Sialidases: structures, biological significance and therapeutic potential.
references: Investigation of the stability of thiosialosides toward hydrolysis by sialidases using NMR spectroscopy.
references: Multivalency and the mode of action of bacterial sialidases.
references: Sialic acid recognition by Vibrio cholerae neuraminidase.
references: 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.
references: Characterization of Vibrio cholerae neuraminidase by a novel mechanism-based fluorescent labeling reagent.
comment: This enzyme belongs to the glycosidase family-33. This enzyme is composed of three domains. The central catalytic domain is flanked by two lectin-like domains. The catalytic domain of this enzyme is homologous to other glycosidase family-33 neuramidases (T00065 in EzCatDB). Although this enzyme binds two calcium ions, they are not involved in catalysis. Since the active site of this enzyme is conserved and the same as that of its homologous enzyme, sialidase from Micromonospora viridifaciens (T00065 in EzCatDB), the catalytic mechanism of this enzyme is the same as that of the homologous enzyme. Asp250 acts as a general acid-base, whilst Tyr740 acts as a nucleophile.

Jelly Rolls
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.60.120.200

Neuraminidase
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.120.10.10
catalytic domain: index.html

N-Glycan degradation
type: KeggPathway
references: KEGG:MAP00511

Sphingolipid metabolism
type: KeggPathway
references: KEGG:MAP00600

Glycan structures - degradation
type: KeggPathway
references: KEGG:MAP01032

Calcium
type: KeggCofactor
references: KEGG:C00076
compound type: divalent metal (Ca2+, Mg2+)
references: CHEBI:29108
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

GT1b
type: KeggSubstrate
references: KEGG:C06140
compound type: amide group
compound type: carbohydrate
compound type: carboxyl group
compound type: lipid
compound type: polysaccharide
type: KeggProduct

H2O
type: KeggSubstrate
references: KEGG:C00001
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

GM3
type: KeggSubstrate
references: KEGG:C04730
compound type: amide group
compound type: carbohydrate
compound type: carboxyl group
compound type: lipid
compound type: polysaccharide

N-Acetylneuraminyl-galactosylceramide
type: KeggSubstrate
references: KEGG:C06128
compound type: amide group
compound type: carbohydrate
compound type: carboxyl group
compound type: lipid
compound type: polysaccharide

N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
type: KeggSubstrate
references: KEGG:C04884
compound type: amide group
compound type: carbohydrate
compound type: carboxyl group
compound type: lipid
compound type: polysaccharide

N-Acetylneuraminyl-D-galactosyl-N-acetyl-D-galactosaminyl-(N- acetylneuraminyl)-D-galactosyl-D-glucosylceramide
type: KeggSubstrate
references: KEGG:C04927
compound type: amide group
compound type: carbohydrate
compound type: carboxyl group
compound type: lipid
compound type: polysaccharide

GQ1
type: KeggSubstrate
references: KEGG:C06139
compound type: amide group
compound type: carbohydrate
compound type: carboxyl group
compound type: lipid
compound type: polysaccharide

N-Acetylneuraminate
type: KeggProduct
references: KEGG:C00270
compound type: amide group
compound type: carbohydrate
compound type: carboxyl group
references: CHEBI:17012
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

beta-D-Galactosyl-1,4-beta-D-glucosylceramide
type: KeggProduct
references: KEGG:C01290
compound type: amide group
compound type: carbohydrate
compound type: lipid
compound type: polysaccharide

Galactosylceramide
type: KeggProduct
references: KEGG:C02686
compound type: amide group
compound type: carbohydrate
compound type: lipid

GA2
type: KeggProduct
references: KEGG:C06135
compound type: amide group
compound type: carbohydrate
compound type: lipid
compound type: polysaccharide

D-Galactosyl-N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
type: KeggProduct
references: KEGG:C04911
compound type: amide group
compound type: carbohydrate
compound type: carboxyl group
compound type: lipid
compound type: polysaccharide

GD1b
type: KeggProduct
references: KEGG:C06141
compound type: amide group
compound type: carbohydrate
compound type: carboxyl group
compound type: lipid
compound type: polysaccharide

1kitA02
type: Pdb
references: 1kit
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1kit
catalytic residue: ASP 250;GLU 619;TYR 740
cofactor binding residue: ALA 253;ASN 256;ASP 289;THR 313(Calcium-1);PRO 548;ASP 621;ASP 682;ALA 683(Calcium-2)

1w0oA02
type: Pdb
references: 1w0o
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1w0o
catalytic residue: ASP 250;GLU 619;TYR 740
cofactor binding residue: ALA 253;ASN 256;ASP 289;THR 313(Calcium-1);PRO 548;ASP 621;ASP 682;ALA 683(Calcium-2)

1w0pA02
type: Pdb
references: 1w0p
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1w0p
catalytic residue: ASP 250;GLU 619;TYR 740
cofactor binding residue: ALA 253;ASN 256;ASP 289;THR 313(Calcium-1);PRO 548;ASP 621;ASP 682;ALA 683(Calcium-2)

2,3-Didehydro-2-deoxysialic acids structurally varied at C-5 and their behaviour towards the sialidase from Vibrio cholerae.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1797392
journal: Carbohydr Res
volume: 216
pages: 61-6
published year: 1991
authors:
  item: Schreiner E
  item: Zbiral E
  item: Kleineidam RG
  item: Schauer R

Purification, crystallization and preliminary crystallographic study of neuraminidase from Vibrio cholerae and Salmonella typhimurium LT2.
type: BibliographicResource
comment: CHARACTERIZATION, AND X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
medline id: 92389334
references: http://www.ncbi.nlm.nih.gov/pubmed/1518058
journal: J Mol Biol
volume: 226
pages: 1287-90
published year: 1992
authors:
  item: Taylor G
  item: Vimr E
  item: Garman E
  item: Laver G
references: P37060

A kinetic-isotope-effect study of catalysis by Vibrio cholerae neuraminidase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8379920
journal: Biochem J
volume: 294
pages: 653-6
published year: 1993
authors:
  item: Guo X
  item: Sinnott ML

Crystal structure of Vibrio cholerae neuraminidase reveals dual lectin-like domains in addition to the catalytic domain.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
medline id: 95006320
references: http://www.ncbi.nlm.nih.gov/pubmed/7922030
journal: Structure
volume: 2
pages: 535-44
published year: 1994
authors:
  item: Crennell S
  item: Garman E
  item: Laver G
  item: Vimr E
  item: Taylor G
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P37060

Sialidases: structures, biological significance and therapeutic potential.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8994884
journal: Curr Opin Struct Biol
volume: 6
pages: 830-7
published year: 1996
authors:
  item: Taylor G

Investigation of the stability of thiosialosides toward hydrolysis by sialidases using NMR spectroscopy.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10822584
journal: Org Lett
volume: 1
pages: 443-6
published year: 1999
authors:
  item: Wilson JC
  item: Kiefel MJ
  item: Angus DI
  item: von Itzstein M

Multivalency and the mode of action of bacterial sialidases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12797770
journal: J Am Chem Soc
volume: 125
pages: 7154-5
published year: 2003
authors:
  item: Thobhani S
  item: Ember B
  item: Siriwardena A
  item: Boons GJ

Sialic acid recognition by Vibrio cholerae neuraminidase.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/15226294
journal: J Biol Chem
volume: 279
pages: 40819-26
published year: 2004
authors:
  item: Moustafa I
  item: Connaris H
  item: Taylor M
  item: Zaitsev V
  item: Wilson JC
  item: Kiefel MJ
  item: von Itzstein M
  item: Taylor G
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

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.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15211517
journal: Proteins
volume: 56
pages: 346-53
published year: 2004
authors:
  item: Haselhorst T
  item: Wilson JC
  item: Thomson RJ
  item: McAtamney S
  item: Menting JG
  item: Coppel RL
  item: von Itzstein M

Characterization of Vibrio cholerae neuraminidase by a novel mechanism-based fluorescent labeling reagent.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/16128567
journal: Biochemistry
volume: 44
pages: 11669-75
published year: 2005
authors:
  item: Hinou H
  item: Kurogochi M
  item: Shimizu H
  item: Nishimura S

TransitionStateAnalogue
pdb: 1w0oA02
ligand het code: DAN

ReferenceForCatalyticMechanism
reference index: 4
reference section: p.539-541

ReferenceForCatalyticMechanism
reference index: 9
reference section: Scheme 1, p.348