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 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, to produce β-glucose and Glc₂Man₉GlcNAc₂. 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 [3, 5].

Three-dimensional structures

The crystal structures of 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 [3, 5]. This similarity had been predicted on the basis of sequence comparison, before their crystal structures were available [6].

Family Firsts

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

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. Gibson RP, Gloster TM, Roberts S, Warren RA, Storch de Gracia I, García A, Chiara JL, and Davies GJ. (2007). Molecular basis for trehalase inhibition revealed by the structure of trehalase in complex with potent inhibitors. Angew Chem Int Ed Engl. 2007;46(22):4115-9. DOI:10.1002/anie.200604825 |
6. 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 |