Glycoside Hydrolase Family 63

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• Author: ^^^Takashi Tonozuka^^^
• Responsible Curator: ^^^Takashi Tonozuka^^^

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Glycoside Hydrolase Family GH63
Clan	GH-G
Mechanism	inverting
Active site residues	Inferred
CAZy DB link
https://www.cazy.org/GH63.html

Substrate specificities

Glycoside hydrolases of GH63 are exo-acting α-glucosidases. Eukaryotic members of this family are Processing α-Glucosidase I enzymes (mannosyl-oligosaccharide glucosidase, EC 3.2.1.106), which specifically hydrolyze the terminal α-1,2-glucosidic linkage in the N-linked oligosaccharide precursor, Glc₃Man₉GlcNAc₂, to produce β-glucose and Glc₂Man₉GlcNAc₂. Processing α-Glucosidase I thus plays a critical role in the maturation of eukaryotic N-glycans. The enzymatic properties of Cwh41p, a Processing α-glucosidase I from Saccharomyces cerevisiae, have been intensively studied [1] (also reviewed in [2]).

Genes encoding GH63 enzymes have also been found in archaea and bacteria, but their natural substrates are still unclear, as these organisms are not known to produce eukaryotic N-linked oligosacharides. A bacterial GH63 enzyme, Escherichia coli YgjK, demonstrated the highest activity toward the α-1,3-glucosidic linkage of nigerose (Glc-α-1,3-Glc) among the commercially available sugars tested [3].

Kinetics and Mechanism

Family GH63 enzymes are inverting enzymes, as first shown by NMR on a processing α-glucosidase I from S. cerevisiae [4].

Catalytic Residues

The catalytic residues were inferred by comparing the catalytic (α/α)₆ barrel domain of the GH63 enzyme, E. coli YgjK, with those of GH15 and GH37 enzymes. In the case of GH37 and GH63, both of which belong to clan GH-G, the catalytic general acid is predicted as an Asp residue (Asp501 in E. coli YgjK), and the general base is considered to be a Glu residue (Glu727 in E. coli YgjK) [3]. Although both of the corresponding residues of GH15, which belongs to clan GH-L, are identified as Glu residues, the positions of the catalytic residues of GH15, GH37, and GH63 are highly conserved [3, 5].

Three-dimensional structures

The crystal structures of the bacterial GH63 proteins, E. coli YgjK [3] (multiple PDB entries) and Thermus thermophilus uncharacterised protein TTHA0978 (PDB 2z07), have been reported. The catalytic domain consists of an (α/α)₆ barrel fold. The main chain of the (α/α)₆ barrel domain shares high structural similarity with those of GH15, GH37, GH65, and GH94 [3, 5]. This similarity had been predicted on the basis of sequence comparison, before their crystal structures were available [6].

Family Firsts

First gene cloning

Human processing α-glucosidase I [7].

First stereochemistry determination

Processing α-glucosidase I from Saccharomyces cerevisiae (Cwh41p) [4].

First general acid residue identification

Inferred from structural comparison [3].

First general base residue identification

Inferred from structural comparison [3].

First 3-D structure

Escherichia coli YgjK, an enzyme showing the highest activity for the α-1,3-glucosidic linkage of nigerose [3].

References

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