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 this family are exo-acting inverting enzymes. The most commonly characterized activity of the eukaryotic enzymes is processing α-glucosidase I (EC 3.2.1.106), which specifically hydrolyzes the terminal α-1,2-glucosidic linkage in the N-linked oligosaccharide precursor, Glc₃Man₉GlcNAc₂. The enzymatic properties of Cwh41p, a processing α-glucosidase I from Saccharomyces cerevisiae, have been most intensively studied ( [1], also reviewed in [2] ).

Genes for the GH63 enzymes have also been found in archaea and bacteria, but archaea and bacteria have been reported not to produce eukaryotic N-linked oligosacharides, and the principal substrates of archaeal and bacterial GH63 enzymes are still unclear. A bacterial GH63 enzyme, Escherichia coli YgjK, showed the highest activity for the α-1,3-glucosidic linkage of nigerose (Glc-α-1,3-Glc) among commercially available sugars [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 (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 as a Glu residue (Glu727 in E. coli YgjK) [3]. Although the two corresponding residues of GH15 (belonging to clan GH-L) are identified as two Glu residues, the positions of the catalytic residues of GH15, GH37, and GH63 are highly conserved.

Three-dimensional structures

The crystal structures of two bacterial GH63 proteins, E. coli YgjK [3] and Thermus thermophilus uncharacterised protein TTHA0978 (PDB 2z07), have been reported. The catalytic domain consists of a (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. This similarity was predicted before their crystal structures were available [5].

Family Firsts

First stereochemistry determination

Cwh41p, a processing α-glucosidase I from Saccharomyces cerevisiae [4].

First catalytic nucleophile identification

Cite some reference here, with a short (1-2 sentence) explanation [3].

First general acid/base residue identification

Cite some reference here, with a short (1-2 sentence) explanation [3].

First 3-D structure

Cite some reference here, with a short (1-2 sentence) explanation [3].

References

1. Dhanawansa R, Faridmoayer A, van der Merwe G, Li YX, and Scaman CH. (2002). Overexpression, purification, and partial characterization of Saccharomyces cerevisiae processing alpha glucosidase I. Glycobiology. 2002;12(3):229-34. DOI:10.1093/glycob/12.3.229 |
2. Herscovics A (1999). Processing glycosidases of Saccharomyces cerevisiae. Biochim Biophys Acta. 1999;1426(2):275-85. DOI:10.1016/s0304-4165(98)00129-9 |
3. Kurakata Y, Uechi A, Yoshida H, Kamitori S, Sakano Y, Nishikawa A, and Tonozuka T. (2008). Structural insights into the substrate specificity and function of Escherichia coli K12 YgjK, a glucosidase belonging to the glycoside hydrolase family 63. J Mol Biol. 2008;381(1):116-28. DOI:10.1016/j.jmb.2008.05.061 |
4. Palcic MM, Scaman CH, Otter A, Szpacenko A, Romaniouk A, Li YX, and Vijay IK. (1999). Processing alpha-glucosidase I is an inverting glycosidase. Glycoconj J. 1999;16(7):351-5. DOI:10.1023/a:1007096011392 |
5. Stam MR, Blanc E, Coutinho PM, and Henrissat B. (2005). Evolutionary and mechanistic relationships between glycosidases acting on alpha- and beta-bonds. Carbohydr Res. 2005;340(18):2728-34. DOI:10.1016/j.carres.2005.09.018 |