DB code: D00664
| RLCP classification | 1.30.35890.994 : Hydrolysis | |
|---|---|---|
| CATH domain | 3.20.20.70 : TIM Barrel | Catalytic domain |
| 2.60.40.1180 : Immunoglobulin-like | ||
| E.C. | 3.2.1.22 | |
| CSA | 1uas | |
| M-CSA | 1uas | |
| MACiE | ||
| CATH domain | Related DB codes (homologues) |
|---|---|
| 2.60.40.1180 : Immunoglobulin-like | M00113 T00307 D00165 D00176 D00665 D00863 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 D00665 D00804 D00863 T00089 |
| Uniprot Enzyme Name | UniprotKB | Protein name | Synonyms | CAZy | Pfam | RefSeq |
|---|---|---|---|---|---|
| Q92456 |
|
Alpha-galactosidase
EC 3.2.1.22 |
GH27
(Glycoside Hydrolase Family 27)
|
PF02065
(Melibiase)
[Graphical View] |
|
| Q9FXT4 |
Alpha-galactosidase
|
EC
3.2.1.22
Alpha-D-galactoside galactohydrolase Melibiase |
GH27
(Glycoside Hydrolase Family 27)
|
PF02065
(Melibiase)
[Graphical View] |
NP_001064939.2
(Protein)
NM_001071474.2 (DNA/RNA sequence) |
| P06280 |
Alpha-galactosidase A (EC 3.2.1.22) (Alpha-D-galactosidase A) (Alpha-D-galactoside galactohydrolase) (Melibiase)AltName: INN=Agalsidase;
|
None |
GH27
(Glycoside Hydrolase Family 27)
|
PF02065
(Melibiase)
[Graphical View] |
NP_000160.1
(Protein)
NM_000169.2 (DNA/RNA sequence) |
| 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 |
|---|---|---|---|---|---|
| Q92456 | Q92456_HYPJE | ||||
| Q9FXT4 | AGAL_ORYSA | Hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-D-galactosides, including galactose oligosaccharides, galactomannans and galactohydrolase. | |||
| P06280 | AGAL_HUMAN | Hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-D-galactosides, including galactose oligosaccharides, galactomannans and galactohydrolase. | Homodimer. | Lysosome. |
| 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 | L00045 | C05402 | C00883 | C00001 | C00984 | L00045 | C00031 | C02492 | I00062 | |||||
| E.C. | ||||||||||||||
| Compound | alpha-D-galactoside | Melibiose | galactomannan | H2O | alpha-D-Galactose | alpha-D-galactoside | D-Glucose | 1,4-beta-D-Mannan | Peptidyl-ASP-beta-D-galactose | |||||
| Type | polysaccharide | polysaccharide | polysaccharide | H2O | carbohydrate | polysaccharide | carbohydrate | polysaccharide | ||||||
| ChEBI |
28053 28053 |
27680 27680 |
15377 15377 |
28061 28061 |
4167 4167 |
|||||||||
| PubChem |
440658 440658 |
439336 439336 |
22247451 962 22247451 962 |
439357 439357 |
5793 5793 |
|||||||||
| 1sznA01 |
|
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Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1t0oA01 |
|
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|
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Unbound | Unbound | Unbound | Analogue:GAL | Unbound | Unbound | Unbound | Unbound | |
| 1uasA01 |
|
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|
|
Unbound | Unbound | Unbound | Bound:GLA | Unbound | Unbound | Unbound | Unbound | |
| 1r46A01 |
|
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Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1r46B01 |
|
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|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1r47A01 |
|
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|
Unbound | Unbound | Unbound | Analogue:GAL | Unbound | Unbound | Unbound | Unbound | |
| 1r47B01 |
|
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|
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Unbound | Unbound | Unbound | Analogue:GAL | Unbound | Unbound | Unbound | Unbound | |
| 3gxnA01 |
|
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|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3gxnB01 |
|
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|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3gxpA01 |
|
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|
Unbound | Unbound | Unbound | Bound:GLA | Unbound | Unbound | Unbound | Unbound | |
| 3gxpB01 |
|
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|
|
Unbound | Unbound | Unbound | Bound:GLA | Unbound | Unbound | Unbound | Unbound | |
| 3gxtA01 |
|
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|
|
Unbound | Unbound | Unbound | Analogue:NOJ | Unbound | Unbound | Unbound | Unbound | |
| 3gxtB01 |
|
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Unbound | Unbound | Unbound | Analogue:NOJ | Unbound | Unbound | Unbound | Unbound | |
| 3hg2A01 |
|
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|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg2B01 |
|
|
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|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg3A01 |
|
|
|
|
|
Unbound | Bound:GLA-GLC | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg3B01 |
|
|
|
|
|
Unbound | Bound:GLA-GLC | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg4A01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Intermediate-analogue:7JZ | |
| 3hg4B01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Intermediate-analogue:7JZ | |
| 3hg5A01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Bound:GLA | Unbound | Unbound | Unbound | Unbound | |
| 3hg5B01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Bound:GLA | Unbound | Unbound | Unbound | Unbound | |
| 1sznA02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1t0oA02 |
|
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|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1uasA02 |
|
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|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1r46A02 |
|
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|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1r46B02 |
|
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Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1r47A02 |
|
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Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1r47B02 |
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|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3gxnA02 |
|
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|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3gxnB02 |
|
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|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3gxpA02 |
|
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|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3gxpB02 |
|
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|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3gxtA02 |
|
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|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3gxtB02 |
|
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Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg2A02 |
|
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Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg2B02 |
|
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|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg3A02 |
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Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg3B02 |
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Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg4A02 |
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Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg4B02 |
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Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg5A02 |
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Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hg5B02 |
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Unbound | Unbound | Unbound | Unbound | 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 | |||||
| 1sznA01 |
|
|
|
|
|
ASP 54;TYR 96;ASP 132;ARG 222;ASP 226 | ||||
| 1t0oA01 |
|
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|
|
|
ASP 54;TYR 96;ASP 132;ARG 222;ASP 226 | ||||
| 1uasA01 |
|
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ASP 51;TYR 93;ASP 130;ARG 181;ASP 185 | ||||
| 1r46A01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 1r46B01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 1r47A01 |
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 1r47B01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3gxnA01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3gxnB01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3gxpA01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3gxpB01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3gxtA01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3gxtB01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3hg2A01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3hg2B01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3hg3A01 |
|
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ASP 92;TYR 134;;ARG 227;ASP 231 | mutant D170A | |||
| 3hg3B01 |
|
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ASP 92;TYR 134;;ARG 227;ASP 231 | mutant D170A | |||
| 3hg4A01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3hg4B01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3hg5A01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 3hg5B01 |
|
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ASP 92;TYR 134;ASP 170;ARG 227;ASP 231 | ||||
| 1sznA02 |
|
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| 1t0oA02 |
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| 1uasA02 |
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| 1r46A02 |
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| 1r46B02 |
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| 1r47A02 |
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| 1r47B02 |
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| 3gxnA02 |
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| 3gxnB02 |
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| 3gxpA02 |
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| 3gxpB02 |
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| 3gxtA02 |
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| 3gxtB02 |
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| 3hg2A02 |
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| 3hg2B02 |
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| 3hg3A02 |
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| 3hg3B02 |
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| 3hg4A02 |
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| 3hg4B02 |
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| 3hg5A02 |
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| 3hg5B02 |
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| 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, |
| 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, |
| 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, |
| 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, Alpha-galactosidases can be classified into glycosidase family-4, This enzyme is homologous to alpha-N-acetylgalactosaminidase (EC 3.2.1.49; D00665 in EzCatDB) and a counterpart enzyme from fungi (EC 3.2.1.22; D00863), According to the literature [5], (0) Considering the conservation and relative location of active-site residues, (1) Asp231 (of 1r46) acts as a general acid to protonate the leaving group. (2) Meanwhile, (3) Asp231 acts as a general base to deprotonate a water molecule, (4) The activated water makes a nucleophilic attack on the C1 atom of the covalent intermediate, |
| Created | Updated |
|---|---|
| 2010-03-05 | 2012-02-07 |