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Glycoside Hydrolase Family 89
- Author: ^^^Elizabeth Ficko-Blean^^^
- Responsible Curator: ^^^Alisdair Boraston^^^
| Glycoside Hydrolase Family GH89 | |
| Clan | none |
| Mechanism | Retaining |
| Active site residues | known |
| CAZy DB link | |
| http://www.cazy.org/fam/GH89.html | |
Substrate specificities
The family 89 glycoside hydrolases are active as α-N-acetylglucosaminidases. The human lysosomal enzyme, NAGLU, is involved in the degradation of heparan sulfate. Mutations in this enzyme can cause a devastating disease called Sanfilippo syndrome type B which is also called mucopolysaccharidosis IIIB.
Kinetics and Mechanism
Mechanistic and structural data is available on CpGH89, a family 89 glycoside hydrolase produced by Clostridium perfringens. CpGH89 uses a double displacement mechanism to hydrolyze the glycosidic bond which results in retention of stereochemistry at the anomeric carbon.
Catalytic Residues
Two catalytically important glutamate residues have been identified in CpGH89, Glu483 and Glu601. These residues are between 6.1-6.7Å apart which is consistent with a retaining catalytic mechanism. Mutation of Glu601 to an alanine results in an apparent abolishment of activity suggesting this residue is active as the catalytic nucleophile. Glu601 resides below the beta-face of the sugar ring and is 2.8-3.1Å from C1 and appears suitably placed for nucleophilic attack on the anomeric carbon. Mutation of Glu483 to alanine results in much less severe impairments in catalysis suggesting this residue is active as the catalytic acid/base residue. Glu483 is ~3.6Å from C1 and appears to be positioned in such a way that it would be capable of forming a hydrogen bond with the glycosidic oxygen of the substrate.
Three-dimensional structures
Family Firsts
- First sterochemistry determination
- Cite some reference here, with a short explanation [1].
- First catalytic nucleophile identification
- First general acid/base residue identification
- First 3-D structure