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 15377	47952 47952
PubChem		22247451 962 22247451 962	94715 94715

1bhgA01	Unbound		Unbound	Unbound
1bhgB01	Unbound		Unbound	Unbound
1bhgA02	Unbound		Unbound	Unbound
1bhgB02	Unbound		Unbound	Unbound
1bhgA03	Unbound		Unbound	Unbound
1bhgB03	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
1bhgB01
1bhgA02
1bhgB02
1bhgA03	GLU 451;TYR 504;GLU 540
1bhgB03	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).

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