DB code: T00066

RLCP classification 1.30.36210.971 : Hydrolysis
CATH domain 2.60.120.260 : Jelly Rolls
2.60.40.320 : Immunoglobulin-like
3.20.20.80 : TIM Barrel Catalytic domain
E.C. 3.2.1.31
CSA 1bhg
M-CSA 1bhg
MACiE

CATH domain Related DB codes (homologues)
2.60.120.260 : Jelly Rolls M00124 T00005 T00065
2.60.40.320 : Immunoglobulin-like M00026
3.20.20.80 : TIM Barrel S00202 S00210 S00748 S00906 S00907 S00911 S00912 S00915 M00134 M00160 D00479 S00204 S00205 S00206 S00207 S00203 S00208 S00209 S00211 S00213 S00214 M00113 T00307 D00165 D00166 D00169 D00176 D00501 D00502 D00503 D00844 D00861 D00864 M00026 M00112 M00193 M00346 T00057 T00062 T00063 T00067

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq CAZy Pfam
P08236 Beta-glucuronidase
EC 3.2.1.31
Beta-G1
NP_000172.2 (Protein)
NM_000181.3 (DNA/RNA sequence)
GH2 (Glycoside Hydrolase Family 2)
PF00703 (Glyco_hydro_2)
PF02836 (Glyco_hydro_2_C)
PF02837 (Glyco_hydro_2_N)
[Graphical View]

KEGG enzyme name
beta-glucuronidase
beta-glucuronide glucuronohydrolase glucuronidase
exo-beta-D-glucuronidase
ketodase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P08236 BGLR_HUMAN A beta-D-glucuronoside + H(2)O = D-glucuronate + an alcohol. Homotetramer. Lysosome.

KEGG Pathways
Map code Pathways E.C.
MAP00040 Pentose and glucuronate interconversions
MAP00500 Starch and sucrose metabolism
MAP00531 Glycosaminoglycan degradation
MAP00860 Porphyrin and chlorophyll metabolism
MAP00944 Flavone and flavonol biosynthesis
MAP00983 Drug metabolism - other enzymes
MAP01032 Glycan structures - degradation

Compound table
Substrates Products Intermediates
KEGG-id C03033 C00001 C00191 C00069
E.C.
Compound beta-D-Glucuronoside H2O D-Glucuronate Alcohol
Type carbohydrate,carboxyl group H2O carbohydrate,carboxyl group carbohydrate
ChEBI 15377
47952
PubChem 962
22247451
94715
1bhgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1bhgB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1bhgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1bhgB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1bhgA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1bhgB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [4] & [7] (see [Comments])

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bhgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1bhgB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1bhgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1bhgB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1bhgA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 451;TYR 504;GLU 540
1bhgB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 451;TYR 504;GLU 540

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
p.379
[5]
FIG.1, p.34058

References
[1]
Resource
Comments
Medline ID
PubMed ID 5063464
Journal J Biol Chem
Year 1972
Volume 247
Pages 2644-9
Authors Wang CC, Touster O
Title Studies of catalysis by -glucuronidase. Active site.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2467874
Journal Indian J Biochem Biophys
Year 1988
Volume 25
Pages 319-25
Authors Gupta GS, Singh G
Title Catalytic properties and immunoprecipitation of beta-glucuronidase in presence of its IgG and Fab fragments: identification of antigenic domains.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8377186
Journal J Mol Biol
Year 1993
Volume 233
Pages 173-6
Authors Drendel WB, Grubb JH, Sly WS, Chen Z, Mathews FS, Jain S
Title Crystallization and preliminary crystallographic studies of human beta-glucuronidase.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
Medline ID 96185449
PubMed ID 8599764
Journal Nat Struct Biol
Year 1996
Volume 3
Pages 375-81
Authors Jain S, Drendel WB, Chen ZW, Mathews FS, Sly WS, Grubb JH
Title Structure of human beta-glucuronidase reveals candidate lysosomal targeting and active-site motifs.
Related PDB 1bhg
Related UniProtKB P08236
[5]
Resource
Comments
Medline ID
PubMed ID 9852062
Journal J Biol Chem
Year 1998
Volume 273
Pages 34057-62
Authors Wong AW, He S, Grubb JH, Sly WS, Withers SG
Title Identification of Glu-540 as the catalytic nucleophile of human beta-glucuronidase using electrospray mass spectrometry.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10366443
Journal Genomics
Year 1999
Volume 58
Pages 121-8
Authors Fyfe JC, Kurzhals RL, Lassaline ME, Henthorn PS, Alur PR, Wang P, Wolfe JH, Giger U, Haskins ME, Patterson DF, Sun H, Jain S, Yuhki N
Title Molecular basis of feline beta-glucuronidase deficiency: an animal model of mucopolysaccharidosis VII.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10438523
Journal J Biol Chem
Year 1999
Volume 274
Pages 23451-5
Authors Islam MR, Tomatsu S, Shah GN, Grubb JH, Jain S, Sly WS
Title Active site residues of human beta-glucuronidase. Evidence for Glu(540) as the nucleophile and Glu(451) as the acid-base residue.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11124909
Journal J Mol Biol
Year 2001
Volume 305
Pages 331-9
Authors Matsumura I, Ellington AD
Title In vitro evolution of beta-glucuronidase into a beta-galactosidase proceeds through non-specific intermediates.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11786015
Journal J Mol Biol
Year 2002
Volume 315
Pages 325-37
Authors Flores H, Ellington AD
Title Increasing the thermal stability of an oligomeric protein, beta-glucuronidase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 15069062
Journal J Biol Chem
Year 2004
Volume 279
Pages 26462-8
Authors Geddie ML, Matsumura I
Title Rapid evolution of beta-glucuronidase specificity by saturation mutagenesis of an active site loop.
Related PDB
Related UniProtKB

Comments
This family belongs to glycosidase family-2, which has an retaining mechanism (equatorial to equatorial conformation), and also a member of 4/7 superfamily, which has got catalytic residues at the C-terminal ends of beta-4 and beta-7 on the (alpha/beta)8 barrel fold.
According to the literature [4] & [5], Glu451 may act as a general acid, whilst Glu540 acts as a nucleophile. This enzyme must adopt a similar mechanism to that of the other 4/7 superfamily members.
Moreover, comparing the structural data with that of xylanase (E.C. 3.2.1.8) (D00479 in EzCatDB), Tyr504 might stabilize the leaving nucleophile, Glu540, in deglycosylation. On the other hand, Tyr504 might modulate the activity of the nucleophile, according to the data of the other homologous enzyme, beta-glucosidase (E.C. 3.2.1.21) (S00205 in EzCatDB).

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