EzCatDB: D00864
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DB codeD00864
RLCP classification1.30.35885.972 : Hydrolysis
CATH domainDomain 13.20.20.80 : TIM BarrelCatalytic domain
Domain 22.60.40.1180 : Immunoglobulin-like
E.C.3.2.1.45
CSA2f61

CATH domainRelated DB codes (homologues)
2.60.40.1180 : Immunoglobulin-likeM00113,T00307,D00165,D00176,D00664,D00665,D00863,M00112,M00193,M00314,T00057,T00062,T00067
3.20.20.80 : TIM BarrelS00202,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,M00026,M00112,M00193,M00346,T00057,T00062,T00063,T00066,T00067

Enzyme Name
UniProtKBKEGG

Q9BDT0P04062
Protein nameGlucosylceramidaseGlucosylceramidaseGlucosylceramidase
Psychosine hydrolase
Glucosphingosine glucosylhydrolase
GlcCer-beta-glucosidase
beta-D-Glucocerebrosidase
Glucosylcerebrosidase
beta-Glucosylceramidase
Ceramide glucosidase
Glucocerebrosidase
Glucosylsphingosine beta-glucosidase
Glucosylsphingosine beta-D-glucosidase
SynonymsEC 3.2.1.45
Acid beta-glucosidase
Beta-glucocerebrosidase
D-glucosyl-N-acylsphingosine glucohydrolase
EC 3.2.1.45
Acid beta-glucosidase
Alglucerase
Beta-glucocerebrosidase
D-glucosyl-N-acylsphingosine glucohydrolase
Imiglucerase
RefSeqNP_001008997.1 (Protein)
NM_001008997.1 (DNA/RNA sequence)
NP_000148.2 (Protein)
NM_000157.3 (DNA/RNA sequence)
NP_001005741.1 (Protein)
NM_001005741.2 (DNA/RNA sequence)
NP_001005742.1 (Protein)
NM_001005742.2 (DNA/RNA sequence)
PfamPF02055 (Glyco_hydro_30)
[Graphical view]
PF02055 (Glyco_hydro_30)
[Graphical view]
CAZyGH30 (Glycoside Hydrolase Family)
GH30 (Glycoside Hydrolase Family)

KEGG pathways
MAP codePathways
MAP00600Sphingolipid metabolism
MAP01032Glycan structures - degradation

UniProtKB:Accession NumberQ9BDT0P04062
Entry nameGLCM_PANTRGLCM_HUMAN
ActivityD-glucosyl-N-acylsphingosine + H(2)O = D-glucose + N-acylsphingosine.D-glucosyl-N-acylsphingosine + H(2)O = D-glucose + N-acylsphingosine.
SubunitInteracts with SCARB2 (By similarity).Interacts with saposin-C.
Subcellular locationLysosome membrane, Peripheral membrane protein (By similarity). Note=Targeting to lysosomes occurs through an alternative MPR-independent mechanism via SCARB2 (By similarity).Lysosome membrane, Peripheral membrane protein, Lumenal side. Note=Interaction with saposin-C promotes membrane association.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC01190C00001C00031C00195I00122
CompoundD-glucosyl-N-acylsphingosineH2OD-glucoseN-acylsphingosinePeptidyl-Glu-Glucose
Typeamide group,carbohydrate,lipidH2Ocarbohydrateamide group,carbohydrate,lipid
ChEBI
15377
4167


PubChem
962
22247451
5793


             
2vt0A01Unbound UnboundUnboundIntermediate-analogue:CBU
2vt0B01Unbound UnboundUnboundIntermediate-analogue:CBU
1ogsA01Unbound UnboundUnboundUnbound
1ogsB01Unbound UnboundUnboundUnbound
1y7vA01Unbound UnboundUnboundIntermediate-analogue:INS
1y7vB01Unbound UnboundUnboundIntermediate-analogue:INS
2f61A01Unbound UnboundUnboundUnbound
2f61B01Unbound UnboundUnboundUnbound
2j25A01Unbound UnboundUnboundUnbound
2j25B01Unbound UnboundUnboundUnbound
2nsxA01Unbound UnboundUnboundUnbound
2nsxB01Unbound Analogue:IFMUnboundUnbound
2nsxC01Unbound UnboundUnboundUnbound
2nsxD01Unbound Analogue:IFMUnboundUnbound
2nt0A01Unbound UnboundUnboundUnbound
2nt0B01Unbound UnboundUnboundUnbound
2nt0C01Unbound UnboundUnboundUnbound
2nt0D01Unbound UnboundUnboundUnbound
2nt1A01Unbound UnboundUnboundUnbound
2nt1B01Unbound UnboundUnboundUnbound
2nt1C01Unbound UnboundUnboundUnbound
2nt1D01Unbound UnboundUnboundUnbound
2v3dA01Analogue:NBV UnboundUnboundUnbound
2v3dB01Analogue:NBV UnboundUnboundUnbound
2v3eA01Analogue:NND UnboundUnboundUnbound
2v3eB01Analogue:NND UnboundUnboundUnbound
2v3fA01Unbound UnboundUnboundUnbound
2v3fB01Unbound UnboundUnboundUnbound
2wcgA01Unbound Analogue:MT5UnboundUnbound
2wcgB01Unbound Analogue:MT5UnboundUnbound
2wklA01Unbound UnboundUnboundUnbound
2wklB01Unbound UnboundUnboundUnbound
2xwdA01Unbound Analogue:LGSUnboundUnbound
2xwdB01Unbound Analogue:LGSUnboundUnbound
2xweA01Analogue:AMF UnboundUnboundUnbound
2xweB01Analogue:AMF UnboundUnboundUnbound
3gxdA01Unbound UnboundUnboundUnbound
3gxdB01Unbound UnboundUnboundUnbound
3gxdC01Unbound UnboundUnboundUnbound
3gxdD01Unbound UnboundUnboundUnbound
3gxfA01Unbound UnboundUnboundUnbound
3gxfB01Unbound Analogue:IFMUnboundUnbound
3gxfC01Unbound UnboundUnboundUnbound
3gxfD01Unbound Analogue:IFMUnboundUnbound
3gxiA01Unbound UnboundUnboundUnbound
3gxiB01Unbound UnboundUnboundUnbound
3gxiC01Unbound UnboundUnboundUnbound
3gxiD01Unbound UnboundUnboundUnbound
3gxmA01Unbound UnboundUnboundUnbound
3gxmB01Unbound UnboundUnboundUnbound
3gxmC01Unbound UnboundUnboundUnbound
3gxmD01Unbound UnboundUnboundUnbound
3ke0A01Unbound UnboundUnboundUnbound
3ke0B01Unbound UnboundUnboundUnbound
3kehA01Unbound UnboundUnboundUnbound
3kehB01Unbound UnboundUnboundUnbound
2vt0A02Unbound UnboundUnboundUnbound
2vt0B02Unbound UnboundUnboundUnbound
1ogsA02Unbound UnboundUnboundUnbound
1ogsB02Unbound UnboundUnboundUnbound
1y7vA02Unbound UnboundUnboundUnbound
1y7vB02Unbound UnboundUnboundUnbound
2f61A02Unbound UnboundUnboundUnbound
2f61B02Unbound UnboundUnboundUnbound
2j25A02Unbound UnboundUnboundUnbound
2j25B02Unbound UnboundUnboundUnbound
2nsxA02Unbound UnboundUnboundUnbound
2nsxB02Unbound UnboundUnboundUnbound
2nsxC02Unbound UnboundUnboundUnbound
2nsxD02Unbound UnboundUnboundUnbound
2nt0A02Unbound UnboundUnboundUnbound
2nt0B02Unbound UnboundUnboundUnbound
2nt0C02Unbound UnboundUnboundUnbound
2nt0D02Unbound UnboundUnboundUnbound
2nt1A02Unbound UnboundUnboundUnbound
2nt1B02Unbound UnboundUnboundUnbound
2nt1C02Unbound UnboundUnboundUnbound
2nt1D02Unbound UnboundUnboundUnbound
2v3dA02Unbound UnboundUnboundUnbound
2v3dB02Unbound UnboundUnboundUnbound
2v3eA02Unbound UnboundUnboundUnbound
2v3eB02Unbound UnboundUnboundUnbound
2v3fA02Unbound UnboundUnboundUnbound
2v3fB02Unbound UnboundUnboundUnbound
2wcgA02Unbound UnboundUnboundUnbound
2wcgB02Unbound UnboundUnboundUnbound
2wklA02Unbound UnboundUnboundUnbound
2wklB02Unbound UnboundUnboundUnbound
2xwdA02Unbound UnboundUnboundUnbound
2xwdB02Unbound UnboundUnboundUnbound
2xweA02Unbound UnboundUnboundUnbound
2xweB02Unbound UnboundUnboundUnbound
3gxdA02Unbound UnboundUnboundUnbound
3gxdB02Unbound UnboundUnboundUnbound
3gxdC02Unbound UnboundUnboundUnbound
3gxdD02Unbound UnboundUnboundUnbound
3gxfA02Unbound UnboundUnboundUnbound
3gxfB02Unbound UnboundUnboundUnbound
3gxfC02Unbound UnboundUnboundUnbound
3gxfD02Unbound UnboundUnboundUnbound
3gxiA02Unbound UnboundUnboundUnbound
3gxiB02Unbound UnboundUnboundUnbound
3gxiC02Unbound UnboundUnboundUnbound
3gxiD02Unbound UnboundUnboundUnbound
3gxmA02Unbound UnboundUnboundUnbound
3gxmB02Unbound UnboundUnboundUnbound
3gxmC02Unbound UnboundUnboundUnbound
3gxmD02Unbound UnboundUnboundUnbound
3ke0A02Unbound UnboundUnboundUnbound
3ke0B02Unbound UnboundUnboundUnbound
3kehA02Unbound UnboundUnboundUnbound
3kehB02Unbound UnboundUnboundUnbound

Active-site residues
resource
literature [5], [7]
pdbCatalytic residuescomment
          
2vt0A01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2vt0B01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
1ogsA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
1ogsB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
1y7vA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
1y7vB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2f61A01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2f61B01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2j25A01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2j25B01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nsxA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nsxB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nsxC01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nsxD01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nt0A01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nt0B01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nt0C01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nt0D01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nt1A01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nt1B01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nt1C01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2nt1D01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2v3dA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2v3dB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2v3eA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2v3eB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2v3fA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2v3fB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2wcgA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2wcgB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2wklA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2wklB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2xwdA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2xwdB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2xweA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
2xweB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxdA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxdB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxdC01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxdD01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxfA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxfB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxfC01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxfD01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxiA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxiB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxiC01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxiD01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxmA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxmB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxmC01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3gxmD01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
 
3ke0A01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
mutant N370S
3ke0B01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
mutant N370S
3kehA01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
mutant N370S
3kehB01ARG 120;ASN 234;GLU 235;HIS 311;TYR 313;GLU 340
mutant N370S
2vt0A02 
 
2vt0B02 
 
1ogsA02 
 
1ogsB02 
 
1y7vA02 
 
1y7vB02 
 
2f61A02 
 
2f61B02 
 
2j25A02 
 
2j25B02 
 
2nsxA02 
 
2nsxB02 
 
2nsxC02 
 
2nsxD02 
 
2nt0A02 
 
2nt0B02 
 
2nt0C02 
 
2nt0D02 
 
2nt1A02 
 
2nt1B02 
 
2nt1C02 
 
2nt1D02 
 
2v3dA02 
 
2v3dB02 
 
2v3eA02 
 
2v3eB02 
 
2v3fA02 
 
2v3fB02 
 
2wcgA02 
 
2wcgB02 
 
2wklA02 
 
2wklB02 
 
2xwdA02 
 
2xwdB02 
 
2xweA02 
 
2xweB02 
 
3gxdA02 
 
3gxdB02 
 
3gxdC02 
 
3gxdD02 
 
3gxfA02 
 
3gxfB02 
 
3gxfC02 
 
3gxfD02 
 
3gxiA02 
 
3gxiB02 
 
3gxiC02 
 
3gxiD02 
 
3gxmA02 
 
3gxmB02 
 
3gxmC02 
 
3gxmD02 
 
3ke0A02 
 
3ke0B02 
 
3kehA02 
 
3kehB02 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]Fig.1, p.886, p.890
[6]Fig.1, p.853
[12]p.4242
[14]Fig.6, p.29055-29057

references
[1]
PubMed ID3927728
JournalAm J Med Genet
Year1985
Volume21
Pages529-49
AuthorsGrabowski GA, Goldblatt J, Dinur T, Kruse J, Svennerholm L, Gatt S, Desnick RJ
TitleGenetic heterogeneity in Gaucher disease: physicokinetic and immunologic studies of the residual enzyme in cultured fibroblasts from non-neuronopathic and neuronopathic patients.
[2]
PubMed ID1714449
JournalJ Biol Chem
Year1991
Volume266
Pages15021-7
AuthorsFabbro D, Grabowski GA
TitleHuman acid beta-glucosidase. Use of inhibitory and activating monoclonal antibodies to investigate the enzyme's catalytic mechanism and saposin A and C binding sites.
[3]
PubMed ID7712292
JournalCurr Opin Struct Biol
Year1994
Volume4
Pages885-92
AuthorsMcCarter JD, Withers SG
TitleMechanisms of enzymatic glycoside hydrolysis.
[4]
PubMed ID8294487
JournalJ Biol Chem
Year1994
Volume269
Pages2283-91
AuthorsGrace ME, Newman KM, Scheinker V, Berg-Fussman A, Grabowski GA
TitleAnalysis of human acid beta-glucosidase by site-directed mutagenesis and heterologous expression.
[5]
PubMed ID7908905
JournalJ Biol Chem
Year1994
Volume269
Pages10975-8
AuthorsMiao S, McCarter JD, Grace ME, Grabowski GA, Aebersold R, Withers SG
TitleIdentification of Glu340 as the active-site nucleophile in human glucocerebrosidase by use of electrospray tandem mass spectrometry.
Related UniProtKBP04062
[6]
PubMed ID8535779
JournalStructure
Year1995
Volume3
Pages853-9
AuthorsDavies G, Henrissat B
TitleStructures and mechanisms of glycosyl hydrolases.
[7]
PubMed ID11087714
JournalGlycobiology
Year2000
Volume10
Pages1217-24
AuthorsFabrega S, Durand P, Codogno P, Bauvy C, Delomenie C, Henrissat B, Martin BM, McKinney C, Ginns EI, Mornon JP, Lehn P
TitleHuman glucocerebrosidase: heterologous expression of active site mutants in murine null cells.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 40-536, GLYCOSYLATION AT ASN-58, AND DISULFIDE BONDS.
PubMed ID12792654
JournalEMBO Rep
Year2003
Volume4
Pages704-9
AuthorsDvir H, Harel M, McCarthy AA, Toker L, Silman I, Futerman AH, Sussman JL
TitleX-ray structure of human acid-beta-glucosidase, the defective enzyme in Gaucher disease.
Related PDB1ogs
Related UniProtKBP04062
[9]
PubMed ID15019270
JournalTrends Pharmacol Sci
Year2004
Volume25
Pages147-51
AuthorsFuterman AH, Sussman JL, Horowitz M, Silman I, Zimran A
TitleNew directions in the treatment of Gaucher disease.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 40-536 IN COMPLEX WITH SYNTHETIC INHIBITOR, ACTIVE SITE.
PubMed ID15817452
JournalJ Biol Chem
Year2005
Volume280
Pages23815-9
AuthorsPremkumar L, Sawkar AR, Boldin-Adamsky S, Toker L, Silman I, Kelly JW, Futerman AH, Sussman JL
TitleX-ray structure of human acid-beta-glucosidase covalently bound to conduritol-B-epoxide. Implications for Gaucher disease.
Related PDB1y7v
Related UniProtKBP04062
[11]
CommentsX-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 40-536, AND GLYCOSYLATION AT ASN-58; ASN-98 AND ASN-185.
PubMed ID17139081
JournalActa Crystallogr D Biol Crystallogr
Year2006
Volume62
Pages1458-65
AuthorsBrumshtein B, Wormald MR, Silman I, Futerman AH, Sussman JL
TitleStructural comparison of differently glycosylated forms of acid-beta-glucosidase, the defective enzyme in Gaucher disease.
Related PDB2j25
Related UniProtKBP04062
[12]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 40-536, CHARACTERIZATION OF GD VARIANTS SER-55; GLN-87; ASN-118; GLN-159; LEU-161; VAL-162; VAL-166; ASN-200; PHE-213; PHE-224; GLU-232; GLU-237; LEU-298; ILE-303; CYS-343; ILE-362; LYS-365; GLY-381; LYS-388; TRP-392; CYS-402; SER-409; VAL-410; HIS-419; LYS-421; ARG-429; LEU-433; SER-436; ASN-438; HIS-448; VAL-455; PRO-483; PRO-500 AND PRO-502, AND MUTAGENESIS OF CYS-43; CYS-57 AND CYS-62.
PubMed ID16293621
JournalJ Biol Chem
Year2006
Volume281
Pages4242-53
AuthorsLiou B, Kazimierczuk A, Zhang M, Scott CR, Hegde RS, Grabowski GA
TitleAnalyses of variant acid beta-glucosidases: effects of Gaucher disease mutations.
Related PDB2f61
Related UniProtKBP04062
[13]
PubMed ID17894779
JournalFEBS J
Year2007
Volume274
Pages4944-50
AuthorsYu Z, Sawkar AR, Kelly JW
TitlePharmacologic chaperoning as a strategy to treat Gaucher disease.
[14]
CommentsX-RAY CRYSTALLOGRAPHY
PubMed ID17666401
JournalJ Biol Chem
Year2007
Volume282
Pages29052-8
AuthorsBrumshtein B, Greenblatt HM, Butters TD, Shaaltiel Y, Aviezer D, Silman I, Futerman AH, Sussman JL
TitleCrystal structures of complexes of N-butyl- and N-nonyl-deoxynojirimycin bound to acid beta-glucosidase: insights into the mechanism of chemical chaperone action in Gaucher disease.
Related PDB2v3e,2v3d
[15]
PubMed ID17713797
JournalJ Mol Model
Year2007
Volume13
Pages1133-9
AuthorsZubrzycki IZ, Borcz A, Wiacek M, Hagner W
TitleThe studies on substrate, product and inhibitor binding to a wild-type and neuronopathic form of human acid-beta-glucosidase.
[16]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 40-536 IN COMPLEXES WITH ISOFAGOMINE, AND SUBCELLULAR LOCATION.
PubMed ID17187079
JournalNat Chem Biol
Year2007
Volume3
Pages101-7
AuthorsLieberman RL, Wustman BA, Huertas P, Powe AC Jr, Pine CW, Khanna R, Schlossmacher MG, Ringe D, Petsko GA
TitleStructure of acid beta-glucosidase with pharmacological chaperone provides insight into Gaucher disease.
Related PDB2nt0,2nt1,2nsx
Related UniProtKBP04062
[17]
CommentsX-RAY CRYSTALLOGRAPHY
PubMed ID17524049
JournalPlant Biotechnol J
Year2007
Volume5
Pages579-90
AuthorsShaaltiel Y, Bartfeld D, Hashmueli S, Baum G, Brill-Almon E, Galili G, Dym O, Boldin-Adamsky SA, Silman I, Sussman JL, Futerman AH, Aviezer D
TitleProduction of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system.
Related PDB2v3f
[18]
PubMed ID18783340
JournalBiol Chem
Year2008
Volume389
Pages1361-9
AuthorsKacher Y, Brumshtein B, Boldin-Adamsky S, Toker L, Shainskaya A, Silman I, Sussman JL, Futerman AH
TitleAcid beta-glucosidase: insights from structural analysis and relevance to Gaucher disease therapy.
Related PDB2vt0
[19]
PubMed ID19374450
JournalBiochemistry
Year2009
Volume48
Pages4816-27
AuthorsLieberman RL, D'aquino JA, Ringe D, Petsko GA
TitleEffects of pH and iminosugar pharmacological chaperones on lysosomal glycosidase structure and stability.
Related PDB3gxd,3gxf,3gxi,3gxm
[20]
PubMed ID19437524
JournalChembiochem
Year2009
Volume10
Pages1480-5
AuthorsBrumshtein B, Aguilar-Moncayo M, Garc?a-Moreno MI, Ortiz Mellet C, Garc?a Fern?ndez JM, Silman I, Shaaltiel Y, Aviezer D, Sussman JL, Futerman AH
Title6-Amino-6-deoxy-5,6-di-N-(N'-octyliminomethylidene)nojirimycin: synthesis, biological evaluation, and crystal structure in complex with acid beta-glucosidase.
Related PDB2wcg
[21]
PubMed ID20980263
JournalJ Biol Chem
Year2011
Volume286
Pages299-308
AuthorsWei RR, Hughes H, Boucher S, Bird JJ, Guziewicz N, Van Patten SM, Qiu H, Pan CQ, Edmunds T
TitleX-ray and biochemical analysis of N370S mutant human acid ¦Â-glucosidase.
Related PDB3ke0,3keh
[22]
PubMed ID21483943
JournalOrg Biomol Chem
Year2011
Volume9
Pages4160-7
AuthorsBrumshtein B, Aguilar-Moncayo M, Benito JM, Garc?a Fernandez JM, Silman I, Shaaltiel Y, Aviezer D, Sussman JL, Futerman AH, Ortiz Mellet C
TitleCyclodextrin-mediated crystallization of acid ¦Â-glucosidase in complex with amphiphilic bicyclic nojirimycin analogues.
Related PDB2xwd,2xwe

comments
This enzyme belongs to glycosidase family-30, with a retaining mechanism.
This enzyme seems to be distantly related to beta-xylosidase (EC 3.2.1.37; D00844 in EzCatDB) from glycosidase family-39, and the catalytic residues of the counterpart enzyme can be superimposed with the corresponding residues. According to the literature [14], [16] and [18], these residues are located at the active site, along with the nucleophilic residue, Glu340, and general acid-base, Glu235.
The reaction may proceeds as follows:
(0) Arg120 and Tyr313 may modulate the activity of catalytic nucleophile, Glu340, whereas His311 may modulate the activity of a general acid-base, Glu235.
(1) Glu235 acts as a general acid to protonate the leaving oxygen, O4 atom at subsite +1, forming an oxocarbenium-ion-like transition-state. The transition-state is stabilized by Asn234 and Tyr313 through hydrogen bonding to the oxygen atoms of glucosyl group. (SN1-like reaction)
(2) Glu340 makes a nucleophilic attack on C1 atom of substrate, glucose, to form a covalent intermediate with the glucose unit.
(3) Glu235 acts as a general base to deprotonate a water molecule, to activate it.
(4) The activated water makes a nucleophilic attack on the C1 atom of the covalent intermediate. Thus, the substitution reaction completes.

createdupdated
2008-05-132012-02-14


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