M00026
type: Enzyme
rlcp: p2
cath: Immunoglobulin-like
cath: Chitobiase; domain 2
cath: TIM Barrel
ec: https://purl.uniprot.org/enzyme/3.2.1.52
csa: 1qba
uniprot: Q54468
kegg enzyme: beta-N-Acetylhexosaminidase
kegg enzyme: Hexosaminidase
kegg pathway: N-Glycan degradation
kegg pathway: Nucleotide sugars metabolism
kegg pathway: Aminosugars metabolism
kegg pathway: Glycosaminoglycan degradation
kegg pathway: Glycosphingolipid biosynthesis - globoseries
kegg pathway: Glycosphingolipid biosynthesis - ganglioseries
kegg substrate: N-Acetyl-beta-D-hexosaminide
kegg substrate: H2O
kegg substrate: Chitobiose
kegg substrate: N-Acetyl-D-glucosaminide
kegg substrate: N-Acetyl-D-galactosaminide
kegg product: N-Acetyl-D-hexosamine
kegg product: N-Acetyl-D-glucosamine
kegg product: N-Acetyl-D-galactosamine
pdb: 1c7sA01
pdb: 1c7tA01
pdb: 1qbaA01
pdb: 1qbbA01
pdb: 1c7sA02
pdb: 1c7tA02
pdb: 1qbaA02
pdb: 1qbbA02
pdb: 1c7sA03
pdb: 1c7tA03
pdb: 1qbaA03
pdb: 1qbbA03
pdb: 1c7sA04
pdb: 1c7tA04
pdb: 1qbaA04
pdb: 1qbbA04
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1c7sA01
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1c7tA01
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1qbaA01
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1qbbA01
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1c7sA02
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1c7tA02
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1qbaA02
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1qbbA02
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1c7sA03
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1c7tA03
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1qbaA03
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1qbbA03
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1c7sA04
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1c7tA04
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1qbaA04
pdb bound state: Unbound
  compound: N-Acetyl-beta-D-hexosaminide
  pdb: 1qbbA04
pdb bound state: Unbound
  compound: Chitobiose
  pdb: 1c7sA01
pdb bound state: Unbound
  compound: Chitobiose
  pdb: 1c7tA01
pdb bound state: Unbound
  compound: Chitobiose
  pdb: 1qbaA01
pdb bound state: Unbound
  compound: Chitobiose
  pdb: 1qbbA01
pdb bound state: Unbound
  compound: Chitobiose
  pdb: 1c7sA02
pdb bound state: Unbound
  compound: Chitobiose
  pdb: 1c7tA02
pdb bound state: Unbound
  compound: Chitobiose
  pdb: 1qbaA02
pdb bound state: Unbound
  compound: Chitobiose
  pdb: 1qbbA02
pdb bound state: Unbound
  compound: Chitobiose
  pdb: 1qbaA03
pdb bound state: Unbound
  compound: Chitobiose
  pdb: 1c7sA04
pdb bound state: Unbound
  compound: Chitobiose
  pdb: 1c7tA04
references: Biochemical and molecular aspects of late-onset GM2-gangliosidosis: B1 variant as a prototype.
references: Crystallization of recombinant chitobiase from Serratia marcescens.
references: Structure-function studies on the chitinolytic enzymes of Serratia marcescens chitinase and chitobiase.
references: N-Acetylglucosaminidase (chitobiase) from Serratia marcescens: gene sequence, and protein production and purification in Escherichia coli.
references: Characterization of glycoproteins and their associated oligosaccharides through the use of endoglycosidases.
references: Bacterial chitobiase structure provides insight into catalytic mechanism and the basis of Tay-Sachs disease.
references: Serratia marcescens chitobiase is a retaining glycosidase utilizing substrate acetamido group participation.
references: Isoenzymes of N-acetyl-beta-hexosaminidase.
references: The structural basis for the susceptibility of gangliosides to enzymatic degradation.
references: Structures of chitobiase mutants complexed with the substrate Di-N-acetyl-d-glucosamine: the catalytic role of the conserved acidic pair, aspartate 539 and glutamate 540.
references: New structural insights into lectin-type proteins of the immune system.
comment: This enzyme belongs to the glycosidase family-20. This enzyme has a retaining mechanism. According to the literature [6], [7] and [10], the reaction of this enzyme proceeds as follows: (0) Asp539 might modulate the general acid, Glu540, by restraining the positioning of Glu540. (1) Glu540 acts as a general acid, to protonate the glycosidic oxygen atom, the O1 atom, leading to the transition state with oxocarbenium ion character. (2) Asp 539 modulate the N-acetyl group of the substrate, by forming a hydrogen bond with the N2 atom of the N-acetyl group. The O7 oxygen atom of the N-acetyl group makes a nucleophilic attack on the C1 atom of the transition state. This nucleophilic substitution seems to be S1-like reaction. (3) A covalent cyclic oxazolinium ion intermediate is formed and stabilized by Asp539, which forms a hydrogen bond with the N2 atom. (4) A water, which is activated by a general base, Glu540, makes a nucleophilic attack on the C1 atom of the intermediate, leading again to the transition state with oxocarbenium ion character. (5) The covalent bond between the C1 atom and the O7 oxygen atom is broken, and finally the product is formed. Thus, Asp539 play multiple roles, a stabilizer for the oxazolinium ion intermediate, and modulators for the N-acetamido group and Glu540 (see [10]).

Immunoglobulin-like
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.60.40.290

Chitobiase; domain 2
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.30.379.10

TIM Barrel
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.20.20.80
catalytic domain: index.html

Immunoglobulin-like
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.60.40.320

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

Nucleotide sugars metabolism
type: KeggPathway
references: KEGG:MAP00520

Aminosugars metabolism
type: KeggPathway
references: KEGG:MAP00530

Glycosaminoglycan degradation
type: KeggPathway
references: KEGG:MAP00531

Glycosphingolipid biosynthesis - globoseries
type: KeggPathway
references: KEGG:MAP00603

Glycosphingolipid biosynthesis - ganglioseries
type: KeggPathway
references: KEGG:MAP00604

N-Acetyl-beta-D-hexosaminide
type: KeggSubstrate
references: KEGG:C03879
compound type: amide group
compound type: carbohydrate

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

Chitobiose
type: KeggSubstrate
references: KEGG:C01674
compound type: amide group
compound type: polysaccharide
references: CHEBI:28681
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

N-Acetyl-D-glucosaminide
type: KeggSubstrate
references: KEGG:C03518
compound type: amide group
compound type: carbohydrate

N-Acetyl-D-galactosaminide
type: KeggSubstrate
references: KEGG:C02848
compound type: amide group
compound type: carbohydrate

N-Acetyl-D-hexosamine
type: KeggProduct
references: KEGG:C03136
compound type: amide group
compound type: carbohydrate
references: CHEBI:21601
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

N-Acetyl-D-glucosamine
type: KeggProduct
references: KEGG:C00140
compound type: amide group
compound type: carbohydrate
references: CHEBI:506227
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

N-Acetyl-D-galactosamine
type: KeggProduct
references: KEGG:C01132
compound type: amide group
compound type: carbohydrate
references: CHEBI:28037
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

1c7sA03
type: Pdb
references: 1c7s
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1c7s
catalytic residue: ;GLU 540
comment: mutant D539A

1c7tA03
type: Pdb
references: 1c7t
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1c7t
catalytic residue: ASP 539;
comment: mutant E540D

1qbaA03
type: Pdb
references: 1qba
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1qba
catalytic residue: ASP 539;GLU 540

1qbbA03
type: Pdb
references: 1qbb
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1qbb
catalytic residue: ASP 539;GLU 540

Biochemical and molecular aspects of late-onset GM2-gangliosidosis: B1 variant as a prototype.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1840099
journal: Dev Neurosci
volume: 13
pages: 288-94
published year: 1991
authors:
  item: Suzuki K
  item: Vanier MT

Crystallization of recombinant chitobiase from Serratia marcescens.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1453472
journal: J Mol Biol
volume: 228
pages: 696-7
published year: 1992
authors:
  item: Tews I
  item: Dauter Z
  item: Oppenheim AB
  item: Vorgias CE

Structure-function studies on the chitinolytic enzymes of Serratia marcescens chitinase and chitobiase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8958090
journal: Ann N Y Acad Sci
volume: 799
pages: 190-2
published year: 1996
authors:
  item: Vorgias CE
  item: Perrakis A
  item: Tews I

N-Acetylglucosaminidase (chitobiase) from Serratia marcescens: gene sequence, and protein production and purification in Escherichia coli.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8621090
journal: Gene
volume: 170
pages: 63-7
published year: 1996
authors:
  item: Tews I
  item: Vincentelli R
  item: Vorgias CE

Characterization of glycoproteins and their associated oligosaccharides through the use of endoglycosidases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/2510544
journal: Anal Biochem
volume: 180
pages: 195-204
published year: 1989
authors:
  item: Maley F
  item: Trimble RB
  item: Tarentino AL
  item: Plummer TH Jr

Bacterial chitobiase structure provides insight into catalytic mechanism and the basis of Tay-Sachs disease.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
medline id: 96266355
references: http://www.ncbi.nlm.nih.gov/pubmed/8673609
journal: Nat Struct Biol
volume: 3
pages: 638-48
published year: 1996
authors:
  item: Tews I
  item: Perrakis A
  item: Oppenheim A
  item: Dauter Z
  item: Wilson KS
  item: Vorgias CE
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: Q54468

Serratia marcescens chitobiase is a retaining glycosidase utilizing substrate acetamido group participation.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9396742
journal: Biochem J
volume: 328
pages: 945-9
published year: 1997
authors:
  item: Drouillard S
  item: Armand S
  item: Davies GJ
  item: Vorgias CE
  item: Henrissat B

Isoenzymes of N-acetyl-beta-hexosaminidase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10698282
journal: Acta Biochim Pol
volume: 46
pages: 739-51
published year: 1999
authors:
  item: Zwierz K
  item: Zalewska A
  item: Zoch-Zwierz A

The structural basis for the susceptibility of gangliosides to enzymatic degradation.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10513893
journal: Biosci Rep
volume: 19
pages: 163-8
published year: 1999
authors:
  item: Sonnino S
  item: Brocca P
  item: Acquotti D
  item: Bernardi A
  item: Raimondi L
  item: Kiso M
  item: Ishida H
  item: Li SC
  item: Li YT

Structures of chitobiase mutants complexed with the substrate Di-N-acetyl-d-glucosamine: the catalytic role of the conserved acidic pair, aspartate 539 and glutamate 540.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/10884356
journal: J Mol Biol
volume: 300
pages: 611-7
published year: 2000
authors:
  item: Prag G
  item: Papanikolau Y
  item: Tavlas G
  item: Vorgias CE
  item: Petratos K
  item: Oppenheim AB
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

New structural insights into lectin-type proteins of the immune system.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11785767
journal: Curr Opin Struct Biol
volume: 11
pages: 635-43
published year: 2001
authors:
  item: Kogelberg H
  item: Feizi T

ReferenceForCatalyticMechanism
reference index: 4
reference section: p.191-192

ReferenceForCatalyticMechanism
reference index: 6
reference section: p.642-643

ReferenceForCatalyticMechanism
reference index: 7
reference section: Scheme 1, p.948

ReferenceForCatalyticMechanism
reference index: 10
reference section: p.613-614