Glycoside Hydrolase Family 63

This page is currently under construction. This means that the Responsible Curator has deemed that the page's content is not quite up to CAZypedia's standards for full public consumption. All information should be considered to be under revision and may be subject to major changes.

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

---

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.

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 |