DB code: T00208

RLCP classification 1.31.36210.99 : Hydrolysis
CATH domain 2.60.120.200 : Jelly Rolls
2.120.10.10 : Neuraminidase Catalytic domain
2.60.120.200 : Jelly Rolls
E.C. 3.2.1.18
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.120.10.10 : Neuraminidase D00173 M00310 T00064 T00065
2.60.120.200 : Jelly Rolls S00148 D00535 D00666 M00185 S00511 T00064

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P0C6E9 Sialidase
EC 3.2.1.18
Neuraminidase
NANase
NP_231419.1 (Protein)
NC_002505.1 (DNA/RNA sequence)
PF09264 (Sial-lect-inser)
[Graphical View]

KEGG enzyme name
exo-alpha-sialidase
neuraminidase
sialidase
alpha-neuraminidase
acetylneuraminidase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P0C6E9 NANH_VIBCH Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates. Monomer (Probable). Secreted. Calcium.

KEGG Pathways
Map code Pathways E.C.
MAP00511 N-Glycan degradation
MAP00600 Sphingolipid metabolism
MAP01032 Glycan structures - degradation

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00076 C06140 C00001 C04730 C06128 C04884 C04927 C06139 C00270 C01290 C02686 C06135 C04911 C06140 C06141
E.C.
Compound Calcium GT1b H2O GM3 N-Acetylneuraminyl-galactosylceramide N-Acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide N-Acetylneuraminyl-D-galactosyl-N-acetyl-D-galactosaminyl-(N- acetylneuraminyl)-D-galactosyl-D-glucosylceramide GQ1 N-Acetylneuraminate beta-D-Galactosyl-1,4-beta-D-glucosylceramide Galactosylceramide GA2 D-Galactosyl-N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide GT1b GD1b
Type divalent metal (Ca2+, Mg2+) amide group,carbohydrate,carboxyl group,lipid,polysaccharide H2O amide group,carbohydrate,carboxyl group,lipid,polysaccharide amide group,carbohydrate,carboxyl group,lipid,polysaccharide amide group,carbohydrate,carboxyl group,lipid,polysaccharide amide group,carbohydrate,carboxyl group,lipid,polysaccharide amide group,carbohydrate,carboxyl group,lipid,polysaccharide amide group,carbohydrate,carboxyl group amide group,carbohydrate,lipid,polysaccharide amide group,carbohydrate,lipid amide group,carbohydrate,lipid,polysaccharide amide group,carbohydrate,carboxyl group,lipid,polysaccharide amide group,carbohydrate,carboxyl group,lipid,polysaccharide amide group,carbohydrate,carboxyl group,lipid,polysaccharide
ChEBI 29108
 29108
 		15377
 15377
 		17012
 17012
PubChem 271
 271
 		22247451
 962
 22247451
 962
 		439197
 439197
1kitA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w0oA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w0pA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1kitA02 Bound:2x_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w0oA02 Bound:2x_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:DAN
1w0pA02 Bound:2x_CA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1kitA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w0oA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w0pA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
See T00065

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1kitA01
1w0oA01
1w0pA01
1kitA02 ASP 250;GLU 619;TYR 740 ALA 253;ASN 256;ASP 289;THR 313(Calcium-1);PRO 548;ASP 621;ASP 682;ALA 683(Calcium-2)
1w0oA02 ASP 250;GLU 619;TYR 740 ALA 253;ASN 256;ASP 289;THR 313(Calcium-1);PRO 548;ASP 621;ASP 682;ALA 683(Calcium-2)
1w0pA02 ASP 250;GLU 619;TYR 740 ALA 253;ASN 256;ASP 289;THR 313(Calcium-1);PRO 548;ASP 621;ASP 682;ALA 683(Calcium-2)
1kitA03
1w0oA03
1w0pA03

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
p.539-541
[9]
Scheme 1, p.348

References
[1]
Resource
Comments
Medline ID
PubMed ID 1797392
Journal Carbohydr Res
Year 1991
Volume 216
Pages 61-6
Authors Schreiner E, Zbiral E, Kleineidam RG, Schauer R
Title 2,3-Didehydro-2-deoxysialic acids structurally varied at C-5 and their behaviour towards the sialidase from Vibrio cholerae.
Related PDB
Related UniProtKB
[2]
Resource
Comments CHARACTERIZATION, AND X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID 92389334
PubMed ID 1518058
Journal J Mol Biol
Year 1992
Volume 226
Pages 1287-90
Authors Taylor G, Vimr E, Garman E, Laver G
Title Purification, crystallization and preliminary crystallographic study of neuraminidase from Vibrio cholerae and Salmonella typhimurium LT2.
Related PDB
Related UniProtKB P37060
[3]
Resource
Comments
Medline ID
PubMed ID 8379920
Journal Biochem J
Year 1993
Volume 294
Pages 653-6
Authors Guo X, Sinnott ML
Title A kinetic-isotope-effect study of catalysis by Vibrio cholerae neuraminidase.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 95006320
PubMed ID 7922030
Journal Structure
Year 1994
Volume 2
Pages 535-44
Authors Crennell S, Garman E, Laver G, Vimr E, Taylor G
Title Crystal structure of Vibrio cholerae neuraminidase reveals dual lectin-like domains in addition to the catalytic domain.
Related PDB 1kit
Related UniProtKB P37060
[5]
Resource
Comments
Medline ID
PubMed ID 8994884
Journal Curr Opin Struct Biol
Year 1996
Volume 6
Pages 830-7
Authors Taylor G
Title Sialidases: structures, biological significance and therapeutic potential.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10822584
Journal Org Lett
Year 1999
Volume 1
Pages 443-6
Authors Wilson JC, Kiefel MJ, Angus DI, von Itzstein M
Title Investigation of the stability of thiosialosides toward hydrolysis by sialidases using NMR spectroscopy.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 12797770
Journal J Am Chem Soc
Year 2003
Volume 125
Pages 7154-5
Authors Thobhani S, Ember B, Siriwardena A, Boons GJ
Title Multivalency and the mode of action of bacterial sialidases.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15226294
Journal J Biol Chem
Year 2004
Volume 279
Pages 40819-26
Authors Moustafa I, Connaris H, Taylor M, Zaitsev V, Wilson JC, Kiefel MJ, von Itzstein M, Taylor G
Title Sialic acid recognition by Vibrio cholerae neuraminidase.
Related PDB 1w0o 1w0p
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 15211517
Journal Proteins
Year 2004
Volume 56
Pages 346-53
Authors Haselhorst T, Wilson JC, Thomson RJ, McAtamney S, Menting JG, Coppel RL, von Itzstein M
Title 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.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 16128567
Journal Biochemistry
Year 2005
Volume 44
Pages 11669-75
Authors Hinou H, Kurogochi M, Shimizu H, Nishimura S
Title Characterization of Vibrio cholerae neuraminidase by a novel mechanism-based fluorescent labeling reagent.
Related PDB
Related UniProtKB

Comments
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.

Created Updated
2006-12-06 2009-02-26