EzCatDB: S00206
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DB codeS00206
RLCP classification1.30.36200.973 : Hydrolysis
CATH domainDomain 13.20.20.80 : TIM BarrelCatalytic domain
E.C.3.2.1.23

CATH domainRelated DB codes (homologues)
3.20.20.80 : TIM BarrelS00202,S00210,S00748,S00906,S00907,S00911,S00912,S00915,M00134,M00160,D00479,S00204,S00205,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,T00066,T00067

Enzyme Name
UniProtKBKEGG

P22498Q9YGA8
Protein nameBeta-galactosidase
beta-galactosidase
lactase (ambiguous)
beta-lactosidase
maxilact
hydrolact
beta-D-lactosidase
S 2107
lactozym
trilactase
beta-D-galactanase
oryzatym
sumiklat
SynonymsLactase
EC 3.2.1.23
Beta-glycosidase
RefSeqNP_344331.1 (Protein)
NC_002754.1 (DNA/RNA sequence)

PfamPF00232 (Glyco_hydro_1)
[Graphical view]
PF00232 (Glyco_hydro_1)
[Graphical view]
CAZyGH1 (Glycoside Hydrolase Family)
GH1 (Glycoside Hydrolase Family)

KEGG pathways
MAP codePathways
MAP00052Galactose metabolism
MAP00511N-Glycan degradation
MAP00531Glycosaminoglycan degradation
MAP00561Glycerolipid metabolism
MAP00600Sphingolipid metabolism
MAP00604Glycosphingolipid biosynthesis - ganglioseries
MAP01032Glycan structures - degradation

UniProtKB:Accession NumberP22498Q9YGA8
Entry nameBGAL_SULSOQ9YGA8_9CREN
ActivityHydrolysis of terminal non-reducing beta-D- galactose residues in beta-D-galactosides.
SubunitHomotetramer.
Subcellular location

Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00602C00001C00962C00602
Compoundbeta-D-GalactosideH2Obeta-D-Galactosebeta-D-Galactoside
TypecarbohydrateH2Ocarbohydratecarbohydrate
ChEBI
15377
27667

PubChem
962
22247451
439353

            
1gowAUnbound UnboundUnbound
1gowBUnbound UnboundUnbound
1qvbAUnbound UnboundUnbound
1qvbBUnbound UnboundUnbound

Active-site residues
resource
literature [2] & [3] (see [Comments])
pdbCatalytic residues
         
1gowAHIS 150;GLU 206;TYR 322;GLU 387
1gowBHIS 150;GLU 206;TYR 322;GLU 387
1qvbAHIS 151;GLU 208;TYR 321;GLU 386
1qvbBHIS 151;GLU 208;TYR 321;GLU 386

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]p.796-797
[4]Fig.2, p.648-6494
[5]p.377-378

references
[1]
PubMed ID7729513
JournalFEBS Lett
Year1995
Volume362
Pages281-5
AuthorsJenkins J, Lo Leggio L, Harris G, Pickersgill R
TitleBeta-glucosidase, beta-galactosidase, family A cellulases, family F xylanases and two barley glycanases form a superfamily of enzymes with 8-fold beta/alpha architecture and with two conserved glutamates near the carboxy-terminal ends of beta-strands four and
[2]
PubMed ID9010932
JournalProtein Eng
Year1996
Volume9
Pages1191-5
AuthorsMoracci M, Capalbo L, Ciaramella M, Rossi M
TitleIdentification of two glutamic acid residues essential for catalysis in the beta-glycosidase from the thermoacidophilic archaeon Sulfolobus solfataricus.
[3]
CommentsX-ray crystallography (2.6 angstroms).
Medline ID97446327
PubMed ID9299327
JournalJ Mol Biol
Year1997
Volume271
Pages789-802
AuthorsAguilar CF, Sanderson I, Moracci M, Ciaramella M, Nucci R, Rossi M, Pearl LH
TitleCrystal structure of the beta-glycosidase from the hyperthermophilic archeon Sulfolobus solfataricus: resilience as a key factor in thermostability.
Related PDB1gow
Related UniProtKBP22498
[4]
PubMed ID9345622
JournalCurr Opin Struct Biol
Year1997
Volume7
Pages645-51
AuthorsWhite A, Rose DR
TitleMechanism of catalysis by retaining beta-glycosyl hydrolases.
[5]
PubMed ID10094493
JournalFEBS Lett
Year1999
Volume445
Pages375-83
AuthorsChi YI, Martinez-Cruz LA, Jancarik J, Swanson RV, Robertson DE, Kim SH
TitleCrystal structure of the beta-glycosidase from the hyperthermophile Thermosphaera aggregans: insights into its activity and thermostability.
[6]
PubMed ID11749955
JournalFEBS Lett
Year2001
Volume509
Pages355-60
AuthorsCorbett K, Fordham-Skelton AP, Gatehouse JA, Davis BG
TitleTailoring the substrate specificity of the beta-glycosidase from the thermophilic archaeon Sulfolobus solfataricus.

comments
This enzyme belongs to the family-1 of glycosidase enzymes, a member family of 4/7 superfamily, which has got the catalytic residues at the C-terminal ends of beta-4 and beta-7 on the (alpha/beta)8 barrel fold [1].
The liteature [2],[3] mentioned that the conserved glucamic acid residue at C-terminal end of beta-7 (Glu387 of 1gow) is the catalytic nucleophile, whilst another conserved residue at C-terminal end of beta-4 (Glu206) might function as a general acid in the first step, in which the covalent intermediate would be formed between the nucleophilic residue and the substrate, and as a general base for a nearby water in the second step, where the intermediate will be hydrolyzed by this water. However, the paper [3] suggested that a conserved histidine residue (His150) at beta-3 might play a role as the general base in the second step, by activating the water, although this residue is not conserved among all the families of 4/7-superfamily.
The literature [4] described general aspects of the catalytic mechanism of retaining beta-glycosyl hydrolases. Accoriding to the paper, the mechanism can be described as follows:
(1) Saccharide binds in a "twisted-boat" conformation.
(2) The beta-1,4 linkage is broken, leading to the formation of a transition state with a slight positive charge at the anomeric carbon, in a "half-chair" conformation, which develops a oxocarbenium-ion-like character.
(3) An approach of the ionic species to the catalytic nucleophile (Glu387 in 1gow) leads to the formation of a covalent intermediate of inverted alpha-configuration in a so-called chair conformation. The aglycon is released and a water molecule diffuses into the vicinity of the acidic residue as a general base.
(4) The covalent intermediate reactivates through an oxocarbenium-ion-like transition state. The general base (Glu206 or His150 in 1gow) abstracts a proton from the incoming water, which in turn carries out a nucleophilic attack on the C1 atom of the residual saccharide.
Moreover, comparing the structural data with that of family-10 enzyme, xylanase (E.C. 3.2.1.8) (D00479 in EzCatDB), Tyr322 (of 1gow) might stabilize the leaving nucleophile, Glu387 in deglycosylation. On the other hand, Tyr322 might modulate the activity of the nucleophile, according to the data of the other family enzyme, beta-glucosidase (E.C. 3.2.1.21) (S00205 in EzCatDB).

createdupdated
2003-02-032009-03-11


Copyright: Nozomi Nagano, JST & CBRC-AIST
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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 2008)
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)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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