DB code: T00065

RLCP classification 1.31.36210.99 : Hydrolysis
CATH domain 2.120.10.10 : Neuraminidase Catalytic domain
2.60.40.10 : Immunoglobulin-like
2.60.120.260 : Jelly Rolls
E.C. 3.2.1.18
CSA 1euu
M-CSA 1euu
MACiE

CATH domain Related DB codes (homologues)
2.120.10.10 : Neuraminidase D00173 M00310 T00064 T00208
2.60.120.260 : Jelly Rolls M00124 T00005 T00066
2.60.40.10 : Immunoglobulin-like M00131 T00257 T00005 M00113 M00127 M00132 M00323 M00325 M00327 M00329 M00330 M00331 M00332 T00307 D00166 D00500 M00112 M00193 T00063 T00067 T00245

Uniprot Enzyme Name
UniprotKB Protein name Synonyms CAZy Pfam
Q02834 Sialidase
EC 3.2.1.18
Neuraminidase
CBM32 (Carbohydrate-Binding Module Family 32)
GH33 (Glycoside Hydrolase Family 33)
PF00754 (F5_F8_type_C)
PF10633 (NPCBM_assoc)
[Graphical View]

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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q02834 NANH_MICVI 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. Secreted.

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 C01330 C04730 C06128 C04884 C04927 C06139 C06140 C00001 C00270 C01290 C02686 C06135 C04911 C06140 C06141
E.C.
Compound Sodium 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 GT1b H2O 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 Oxocarbenium-ion-like transition-state
Type univalent metal (Na+, K+) 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,lipid,polysaccharide H2O 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 29101
15377
17012
PubChem 923
962
22247451
439197
1eurA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eusA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:DAN
1eutA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1euuA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w8nA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:DAN
1w8oA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Analogue:CIT Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2berA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Analogue:SLB Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2bq9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2bq9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2bq9C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eutA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1euuA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w8nA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w8oA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2berA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2bq9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2bq9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2bq9C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eutA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_NA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1euuA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_NA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w8nA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_NA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w8oA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_NA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2berA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_NA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2bq9A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_NA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2bq9B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_NA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2bq9C03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_NA Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;Q02834 & literature [3], [7], [8]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1eurA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 92;GLU 260;TYR 370
1eusA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 92;GLU 260;TYR 370
1eutA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 92;GLU 260;TYR 370
1euuA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 92;GLU 260;TYR 370
1w8nA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;GLU 260;TYR 370 mutant D92G
1w8oA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;GLU 260;TYR 370 mutant D92G
2berA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 92;GLU 260; mutant Y370G
2bq9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 92; ;TYR 370 mutant E260A
2bq9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 92; ;TYR 370 mutant E260A
2bq9C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 92; ;TYR 370 mutant E260A
1eutA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1euuA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1w8nA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1w8oA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2berA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2bq9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2bq9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2bq9C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1eutA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1euuA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1w8nA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1w8oA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2berA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2bq9A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2bq9B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2bq9C03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
p.1199
[7]
p.12682, Scheme 2, p.12687-12689
[8]

References
[1]
Resource
Comments
Medline ID
PubMed ID 1613796
Journal J Mol Biol
Year 1992
Volume 225
Pages 1135-6
Authors Taylor G, Dineley L, Glowka M, Laver G
Title Crystallization and preliminary crystallographic study of neuraminidase from Micromonospora viridifaciens.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7981969
Journal Trends Microbiol
Year 1994
Volume 2
Pages 271-7
Authors Vimr ER
Title Microbial sialidases: does bigger always mean better?
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID 96164436
PubMed ID 8591030
Journal Structure
Year 1995
Volume 3
Pages 1197-205
Authors Gaskell A, Crennell S, Taylor G
Title The three domains of a bacterial sialidase: a beta-propeller, an immunoglobulin module and a galactose-binding jelly-roll.
Related PDB 1eur 1eus 1eut 1euu
Related UniProtKB Q02834
[4]
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
[5]
Resource
Comments
Medline ID
PubMed ID 9147054
Journal Glycobiology
Year 1997
Volume 7
Pages 445-51
Authors Smith LE, Eichinger D
Title Directed mutagenesis of the Trypanosoma cruzi trans-sialidase enzyme identifies two domains involved in its sialyltransferase activity.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10513893
Journal Biosci Rep
Year 1999
Volume 19
Pages 163-8
Authors Sonnino S, Brocca P, Acquotti D, Bernardi A, Raimondi L, Kiso M, Ishida H, Li SC, Li YT
Title The structural basis for the susceptibility of gangliosides to enzymatic degradation.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 14580216
Journal Biochemistry
Year 2003
Volume 42
Pages 12682-90
Authors Watson JN, Dookhun V, Borgford TJ, Bennet AJ
Title Mutagenesis of the conserved active-site tyrosine changes a retaining sialidase into an inverting sialidase.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15527797
Journal FEBS Lett
Year 2004
Volume 577
Pages 265-9
Authors Watson JN, Newstead S, Dookhun V, Taylor G, Bennet AJ
Title Contribution of the active site aspartic acid to catalysis in the bacterial neuraminidase from Micromonospora viridifaciens.
Related PDB 1w8n 1w8o
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 15966735
Journal Biochemistry
Year 2005
Volume 44
Pages 9117-22
Authors Newstead S, Watson JN, Knoll TL, Bennet AJ, Taylor G
Title Structure and mechanism of action of an inverting mutant sialidase.
Related PDB 2ber
Related UniProtKB

Comments
This enzyme belongs to the glycosidase family-33. This enzyme is composed of three domains, the N-terminal catalytic domain, Immunoglobulin-like domain, and the C-terminal F5/8 type C domain.
Although Sodium is included as a cofactor, it is not involved in catalysis. It maintains the conformation of the C-terminal domain.(see [3])
According to the literature [7], the catalytic reaction proceeds as follows:
(1) Asp92 acts as a general acid, to protonate the leaving group, through a water molecule, to give an oxacarbenium ion-like transition state. (SN1-like reaction)
(2) Tyr370, whose pKa is probably modulated by Glu260, makes a nucleophilic attack on the C2 atom of the transition-state, to form a siaryl-enzyme intermediate.
(3) Asp92 acts as a general base, to activate the water.
(4) The activated water makes a nucleophilic attack on the intermediate, to complete the hydrolysis.
###
According to the literature [7], sialyl-based ketal must be much more reactive than ordinary O-glycoside bond.

Created Updated
2005-04-15 2009-02-26