Alpha-galactosidase

 

alpha-galactosidase is a member of the glycoside hydrolase, family 27 and catalyses the hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-D-galactosides, including galactose oligosaccharides, galactomannans and galactolipids such as raffinose, melibiose, and stachyose (in descending order of reactivity).

 

Reference Protein and Structure

Sequence
Q9FXT4 UniProt (3.2.1.22) IPR002241 (Sequence Homologues) (PDB Homologues)
Biological species
Oryza sativa Japonica Group (Japanese rice) Uniprot
PDB
1uas - Crystal structure of rice alpha-galactosidase (1.5 Å) PDBe PDBsum 1uas
Catalytic CATH Domains
3.20.20.70 CATHdb (see all for 1uas)
Click To Show Structure

Enzyme Reaction (EC:3.2.1.22)

water
CHEBI:15377ChEBI
+
melibiose
CHEBI:28053ChEBI
→
D-galactopyranose
CHEBI:4139ChEBI
+
D-glucopyranose
CHEBI:4167ChEBI
Alternative enzyme names: Alpha-D-galactosidase, Alpha-galactosidase A, Alpha-galactoside galactohydrolase, Melibiase,

Enzyme Mechanism

Introduction

Glycoside hydrolase family 27 enzymes are all thought to proceed via a double displacement mechanism with retention of sterochemistry at the anomeric carbon. In this mechanism, one of the two catalytic aspartate residues acts as a nucleophile and becomes attached to the anomeric carbon of the sugar substrate. The other aspartate acts as a general acid/base which activates the catalytic water.

Catalytic Residues Roles

UniProt PDB* (1uas)
Asp185 Asp130A Acts as a nucleophile during the course of the reaction. covalent catalysis
Asp240 Asp185A Acts as a general acid/base. proton shuttle (general acid/base)
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Guce AI et al. (2010), J Biol Chem, 285, 3625-3632. Catalytic mechanism of human alpha-galactosidase. DOI:10.1074/jbc.M109.060145. PMID:19940122.
  2. Bakunina IY et al. (2014), Front Chem, 2, 89-. Stereochemical course of hydrolytic reaction catalyzed by alpha-galactosidase from cold adaptable marine bacterium of genus Pseudoalteromonas. DOI:10.3389/fchem.2014.00089. PMID:25353020.
  3. Fernández-Leiro R et al. (2010), J Biol Chem, 285, 28020-28033. Structural analysis of Saccharomyces cerevisiae alpha-galactosidase and its complexes with natural substrates reveals new insights into substrate specificity of GH27 glycosidases. DOI:10.1074/jbc.M110.144584. PMID:20592022.
  4. Golubev AM et al. (2004), J Mol Biol, 339, 413-422. Crystal structure of alpha-galactosidase from Trichoderma reesei and its complex with galactose: implications for catalytic mechanism. DOI:10.1016/j.jmb.2004.03.062. PMID:15136043.
  5. Fujimoto Z et al. (2003), J Biol Chem, 278, 20313-20318. Crystal Structure of Rice  -Galactosidase Complexed with D-Galactose. DOI:10.1074/jbc.m302292200. PMID:12657636.
  6. Garman SC et al. (2002), Structure, 58, 425-434. The 1.9 Å structure of α-N-acetylgalactosaminidase: molecular basis of glycosidase deficiency diseases. DOI:10.1107/s0108767302095818. PMID:12005440.
  7. Kim WD et al. (2002), Phytochemistry, 61, 621-630. alpha-Galactosidase from cultured rice (Oryza sativa L. var. Nipponbare) cells. PMID:12423882.
  8. Eng CM et al. (1997), Mol Med, 3, 174-182. Fabry disease: thirty-five mutations in the alpha-galactosidase A gene in patients with classic and variant phenotypes. PMID:9100224.
  9. Redonnet-Vernhet I et al. (1996), J Med Genet, 33, 682-688. Uneven X inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the alpha-galactosidase A gene. PMID:8863162.

Step 1.

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Catalytic Residues Roles

Residue Roles
Asp185A proton shuttle (general acid/base)
Asp130A covalent catalysis

Chemical Components

Step 1.

Contributors

Christian Drew, Craig Porter, Gemma L. Holliday