EzCatDB: T00066

DB codeT00066
RLCP classification1.30.36210.971
CATH domainDomain 12.60.120.260
Domain 22.60.40.320
Domain 33.20.20.80Catalytic domain
E.C.3.2.1.31
CSA1bhg

CATH domainRelated DB codes (homologues)
2.60.120.260M00124,T00005,T00065
2.60.40.320M00026
3.20.20.80S00202,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

Enzyme Name
Swiss-protKEGG

P08236
Protein nameBeta-glucuronidasebeta-glucuronidase
beta-glucuronide glucuronohydrolase glucuronidase
exo-beta-D-glucuronidase
ketodase
SynonymsEC 3.2.1.31
Beta-G1

KEGG pathways
MAP codePathways
MAP00040Pentose and glucuronate interconversions
MAP00500Starch and sucrose metabolism
MAP00531Glycosaminoglycan degradation
MAP00860Porphyrin and chlorophyll metabolism
MAP00944Flavone and flavonol biosynthesis
MAP00983Drug metabolism - other enzymes
MAP01032Glycan structures - degradation

Swiss-prot:Accession NumberP08236
Entry nameBGLR_HUMAN
ActivityA beta-D-glucuronoside + H(2)O = D-glucuronate + an alcohol.
SubunitHomotetramer.
Subcellular locationLysosome.
Cofactor


SubstratesProducts
KEGG-idC03033C00001C00191C00069
Compoundbeta-D-GlucuronosideH2OD-GlucuronateAlcohol
Typecarbohydrate,carboxyl groupH2Ocarbohydrate,carboxyl groupcarbohydrate
1bhgA01Unbound
UnboundUnbound
1bhgB01Unbound
UnboundUnbound
1bhgA02Unbound
UnboundUnbound
1bhgB02Unbound
UnboundUnbound
1bhgA03Unbound
UnboundUnbound
1bhgB03Unbound
UnboundUnbound

Active-site residues
resource
literature [4] & [7] (see [Comments])
pdbCatalytic residues
1bhgA01
1bhgB01
1bhgA02
1bhgB02
1bhgA03GLU 451;TYR 504;GLU 540
1bhgB03GLU 451;TYR 504;GLU 540

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]p.379
[5]FIG.1, p.34058

references
[1]
PubMed ID5063464
JournalJ Biol Chem
Year1972
Volume247
Pages2644-9
AuthorsWang CC, Touster O
TitleStudies of catalysis by -glucuronidase. Active site.
[2]
PubMed ID2467874
JournalIndian J Biochem Biophys
Year1988
Volume25
Pages319-25
AuthorsGupta GS, Singh G
TitleCatalytic properties and immunoprecipitation of beta-glucuronidase in presence of its IgG and Fab fragments: identification of antigenic domains.
[3]
PubMed ID8377186
JournalJ Mol Biol
Year1993
Volume233
Pages173-6
AuthorsDrendel WB, Grubb JH, Sly WS, Chen Z, Mathews FS, Jain S
TitleCrystallization and preliminary crystallographic studies of human beta-glucuronidase.
[4]
CommentsX-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
Medline ID96185449
PubMed ID8599764
JournalNat Struct Biol
Year1996
Volume3
Pages375-81
AuthorsJain S, Drendel WB, Chen ZW, Mathews FS, Sly WS, Grubb JH
TitleStructure of human beta-glucuronidase reveals candidate lysosomal targeting and active-site motifs.
Related PDB1bhg
Related Swiss-protP08236
[5]
PubMed ID9852062
JournalJ Biol Chem
Year1998
Volume273
Pages34057-62
AuthorsWong AW, He S, Grubb JH, Sly WS, Withers SG
TitleIdentification of Glu-540 as the catalytic nucleophile of human beta-glucuronidase using electrospray mass spectrometry.
[6]
PubMed ID10366443
JournalGenomics
Year1999
Volume58
Pages121-8
AuthorsFyfe 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
TitleMolecular basis of feline beta-glucuronidase deficiency: an animal model of mucopolysaccharidosis VII.
[7]
PubMed ID10438523
JournalJ Biol Chem
Year1999
Volume274
Pages23451-5
AuthorsIslam MR, Tomatsu S, Shah GN, Grubb JH, Jain S, Sly WS
TitleActive site residues of human beta-glucuronidase. Evidence for Glu(540) as the nucleophile and Glu(451) as the acid-base residue.
[8]
PubMed ID11124909
JournalJ Mol Biol
Year2001
Volume305
Pages331-9
AuthorsMatsumura I, Ellington AD
TitleIn vitro evolution of beta-glucuronidase into a beta-galactosidase proceeds through non-specific intermediates.
[9]
PubMed ID11786015
JournalJ Mol Biol
Year2002
Volume315
Pages325-37
AuthorsFlores H, Ellington AD
TitleIncreasing the thermal stability of an oligomeric protein, beta-glucuronidase.
[10]
PubMed ID15069062
JournalJ Biol Chem
Year2004
Volume279
Pages26462-8
AuthorsGeddie ML, Matsumura I
TitleRapid evolution of beta-glucuronidase specificity by saturation mutagenesis of an active site loop.

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).

createdupdated
2005-04-022009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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