DB code: D00863

RLCP classification	1.30.35890.994 : Hydrolysis
CATH domain	3.20.20.70 : TIM Barrel	Catalytic domain
CATH domain	2.60.40.1180 : Immunoglobulin-like
E.C.	3.2.1.22
CSA
M-CSA
MACiE

CATH domain	Related DB codes (homologues)
2.60.40.1180 : Immunoglobulin-like	M00113 T00307 D00165 D00176 D00664 D00665 D00864 M00112 M00193 M00314 T00057 T00062 T00067
3.20.20.70 : TIM Barrel	S00215 S00217 S00218 S00219 S00532 S00198 S00220 S00745 S00537 S00538 S00539 S00826 S00841 S00235 S00239 S00240 S00243 S00244 S00199 S00200 S00201 S00221 S00222 S00847 S00224 S00225 S00226 D00014 D00029 M00141 T00015 T00239 D00664 D00665 D00804 T00089

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	CAZy	Pfam
Q02402		Alpha-galactosidase	GH27 (Glycoside Hydrolase Family 27)	PF02065 (Melibiase) [Graphical View]

KEGG enzyme name
Alpha-galactosidase Melibiase Alpha-D-galactosidase Alpha-galactosidase A Alpha-galactoside galactohydrolase

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
Q02402	Q02402_9FUNG

KEGG Pathways
Map code	Pathways	E.C.
MAP00052	Galactose metabolism
MAP00561	Glycerolipid metabolism
MAP00600	Sphingolipid metabolism
MAP00603	Glycosphingolipid biosynthesis - globoseries

Compound table
	Substrates		Products		Intermediates
KEGG-id	C00883	C00001	C00984	C02492	I00062
E.C.
Compound	galactomannan	H2O	alpha-D-Galactose	1,4-beta-D-Mannan	Peptidyl-ASP-beta-D-galactose
Type	polysaccharide	H2O	carbohydrate	polysaccharide
ChEBI	27680 27680	15377 15377	28061 28061
PubChem	439336 439336	22247451 962 22247451 962	439357 439357

3a5vA01	Unbound		Unbound	Unbound	Unbound
3a5vA02	Unbound		Unbound	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.
Literature [3], [4], [5], [6], [7], [8], [9] & Swiss-prot;P06280, Q9FXT4

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

3a5vA01	ASP 51;TYR 93;ASP 129;ARG 185;ASP 189
3a5vA02

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[3]	Figure 4
[6]	p.417-419
[9]	FIGURE 1
[10]	Fig.2, Fig.3, p.3627-3630

References
[1]
Resource
Comments
Medline ID
PubMed ID	10933800
Journal	Biochemistry
Year	2000
Volume	39
Pages	9826-36
Authors	Hart DO, He S, Chany CJ 2nd, Withers SG, Sims PF, Sinnott ML, Brumer H 3rd
Title	Identification of Asp-130 as the catalytic nucleophile in the main alpha-galactosidase from Phanerochaete chrysosporium, a family 27 glycosyl hydrolase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	11128583
Journal	Carbohydr Res
Year	2000
Volume	329
Pages	539-47
Authors	Ly HD, Howard S, Shum K, He S, Zhu A, Withers SG
Title	The synthesis, testing and use of 5-fluoro-alpha-D-galactosyl fluoride to trap an intermediate on green coffee bean alpha-galactosidase and identify the catalytic nucleophile.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID	12005440
Journal	Structure
Year	2002
Volume	10
Pages	425-34
Authors	Garman SC, Hannick L, Zhu A, Garboczi DN
Title	The 1.9 A structure of alpha-N-acetylgalactosaminidase: molecular basis of glycosidase deficiency diseases.
Related PDB
Related UniProtKB
[4]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 56-417 IN COMPLEX WITH D-GALACTOSE.
Medline ID
PubMed ID	12657636
Journal	J Biol Chem
Year	2003
Volume	278
Pages	20313-8
Authors	Fujimoto Z, Kaneko S, Momma M, Kobayashi H, Mizuno H
Title	Crystal structure of rice alpha-galactosidase complexed with D-galactose.
Related PDB	1uas
Related UniProtKB	Q9FXT4
[5]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (3.45 ANGSTROMS) OF 32-422 IN COMPLEX WITH PRODUCT, HOMODIMERIZATION, GLYCOSYLATION AT ASN-139; ASN-192 AND ASN-215.
Medline ID
PubMed ID	15003450
Journal	J Mol Biol
Year	2004
Volume	337
Pages	319-35
Authors	Garman SC, Garboczi DN
Title	The molecular defect leading to Fabry disease: structure of human alpha-galactosidase.
Related PDB	1r46 1r47
Related UniProtKB	P06280
[6]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 28-441.
Medline ID
PubMed ID	15136043
Journal	J Mol Biol
Year	2004
Volume	339
Pages	413-22
Authors	Golubev AM, Nagem RA, Brandao Neto JR, Neustroev KN, Eneyskaya EV, Kulminskaya AA, Shabalin KA, Savel'ev AN, Polikarpov I
Title	Crystal structure of alpha-galactosidase from Trichoderma reesei and its complex with galactose: implications for catalytic mechanism.
Related PDB	1szn 1t0o
Related UniProtKB	Q92456
[7]
Resource
Comments
Medline ID
PubMed ID
Journal	Biocatal Biotransformation
Year	2009
Volume	27
Pages	79-89
Authors	Weignerova' L, Simerska' P, Kr(en V
Title	¿-Galactosidases and their applications in biotransformations.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	19374450
Journal	Biochemistry
Year	2009
Volume	48
Pages	4816-27
Authors	Lieberman RL, D'aquino JA, Ringe D, Petsko GA
Title	Effects of pH and iminosugar pharmacological chaperones on lysosomal glycosidase structure and stability.
Related PDB	3gxn 3gxp 3gxt
Related UniProtKB	P06280
[9]
Resource
Comments
Medline ID
PubMed ID	19809163
Journal	Biosci Biotechnol Biochem
Year	2009
Volume	73
Pages	2360-4
Authors	Fujimoto Z, Kaneko S, Kim WD, Park GG, Momma M, Kobayashi H
Title	The tetramer structure of the glycoside hydrolase family 27 alpha-galactosidase I from Umbelopsis vinacea.
Related PDB	3a5v
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID	19940122
Journal	J Biol Chem
Year	2010
Volume	285
Pages	3625-32
Authors	Guce AI, Clark NE, Salgado EN, Ivanen DR, Kulminskaya AA, Brumer H 3rd, Garman SC
Title	Catalytic mechanism of human alpha-galactosidase.
Related PDB	3hg2 3hg3 3hg4 3hg5
Related UniProtKB	P06280

Comments
This enzyme belongs to glycosidase family-27, with a retaining mechanism. Alpha-galactosidases can be classified into glycosidase family-4, 27, 36, 57, 97 and 110 (see [9]). Alpha-galactosidases from eukaryotes are generally classified into glycosidase family-27, whereas prokaryotic alpha-galactosidases are mostly classified into glycosidase family-36 (see [9]). This enzyme is homologous to Alpha-N-acetylgalactosaminidase (EC 3.2.1.49; D00665 in EzCatDB) and a counterpart enzyme from other organisms (EC 3.2.1.22; D00664), which shows different substrate specificities from this enzyme. This enzyme is specific only for galactomannan, whereas the counterpart enzyme is also active toward other alpha-galactosides (see [9]). However, considering the conservation of the active-site structure, this enzyme must catalyze the same reaction type as these homologous enzymes. Asp129 acts as a nucleophile, whereas Asp189 acts as catalytic acid-base.

Comments

This enzyme belongs to glycosidase family-27, with a retaining mechanism.
Alpha-galactosidases can be classified into glycosidase family-4, 27, 36, 57, 97 and 110 (see [9]). Alpha-galactosidases from eukaryotes are generally classified into glycosidase family-27, whereas prokaryotic alpha-galactosidases are mostly classified into glycosidase family-36 (see [9]).
This enzyme is homologous to Alpha-N-acetylgalactosaminidase (EC 3.2.1.49; D00665 in EzCatDB) and a counterpart enzyme from other organisms (EC 3.2.1.22; D00664), which shows different substrate specificities from this enzyme. This enzyme is specific only for galactomannan, whereas the counterpart enzyme is also active toward other alpha-galactosides (see [9]).
However, considering the conservation of the active-site structure, this enzyme must catalyze the same reaction type as these homologous enzymes.
Asp129 acts as a nucleophile, whereas Asp189 acts as catalytic acid-base.

Created	Updated
2010-03-05	2012-02-01