Carbohydrate-active enzymes

This page has been approved by the Responsible Curator as essentially complete. CAZypedia is a living document, so further improvement of this page is still possible. If you would like to suggest an addition or correction, please contact the page's Responsible Curator directly by e-mail.

• Author: Stephen Withers
• Responsible Curator: Spencer Williams

---

Carbohydrates collectively are an immensely important group of biomolecules. The individual monosaccharide units have the potential to be joined together to form oligo- and polysaccharides, with the glycosidic linkage occurring between the anomeric position of one sugar with the hydroxyl group of another. Owing ot the many hydroxy groups on each sugar, the potential for two possible anomeric configurations, and the possibility of different ring sizes (pyranose and furanose are the most common), there is a combinatorially-large number of structures possible. Further, carbohydrates can be linked to ther, non-carbohydrate molecules ot generate a wide range of glycoconjugates. Reflecting this structural diversity, there is a large diversity of enzymes involved in the biosynthesis, modification and catabolism of carbohydrates.

The Carbohydrate Active Enzyme classification is a sequence-based classification of enzymes that are active on carbohydrate structures [1, 2, 3]. The creation of a family requires at least one biochemically-characterized member, and is based on the concept that sequence defines structure, and structure defines function. Generally, but not exclusively, functional properties often extend to other members of the family, and provides a framework upon which to base testable hypotheses of enzyme structure and function.

The major classes of carbohydrate active enzymes within the CAZy classification are:

Glycoside hydrolases (GH)

Strictly speaking, the term 'glycoside hydrolase' refers to enzymes that catalyze the hydrolytic cleavage of the glycosidic bond to give the carbohydrate hemiacetal. However, it is found that sequence-based classification methods often group in enzymes that have non-hydrolytic activities into the same families as hydrolytic enzymes. For example, sequence analysis groups transglycosidases with glycoside hydrolases (e.g. Glycoside Hydrolase Family 13 cyclodextrin glucanotransferases and amylases). According to all available evidencetransglycosidases and glycoside hydrolases use the same mechanism, except that a sugar or some other group, rather than water, acts as the nucleophile.

Similarly, enzymatic formation and cleavage of the bond between two sugars or between a sugar and another group can occur by phosphorolysis to give the sugar-1-phosphate (phosphorylases). Thus ...

An unusual enzyme activity that has been found within or by elimination to give unsaturated sugar products (lyases).

Auxiliary activities (AA)

Key AA ref: [4]

Polysaccharide lyases (PL)

Lyases fall into two mechanistic classes. The largest class is that which cleaves polymers containing uronic acids: most commonly pectins and glycosaminoglycans. These enzymes break the bond between the glycosidic oxygen and the ring carbon of the sugar in the +1 site via an elimination mechanism. This is the group separately classified in CAZY aspolysaccharide lyases (PLs).

Key PL reviews: [5, 6]

Carbohydrate binding modules (CBM)

Key CBM reviews: [7, 8, 9, 10, 11]

Glycosyltransferases (GT)

The principal enzymes that catalyze glycoside synthesis are nucleotide phosphosugar-dependent glycosyltransferases.

Phosphorylases fall into two mechanistic classes: glycoside hydrolase-like and glycosyltransferase-like, and are likewise classified into GH or GT families by sequence comparisons. A second, very small, group of alpha-glucan lyases is found within GH Family 31 and follows a cationic glycoside-hydrolase-like mechanism.

Key GT review: [12]

References

1. Davies, G.J. and Sinnott, M.L. (2008) Sorting the diverse: the sequence-based classifications of carbohydrate-active enzymes. Biochem. J. (A BJ Classics review, online only). DOI: 10.1042/BJ20080382

2. Cantarel BL, Coutinho PM, Rancurel C, Bernard T, Lombard V, and Henrissat B. (2009). The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics. Nucleic Acids Res. 2009;37(Database issue):D233-8. DOI:10.1093/nar/gkn663 |
3. Lombard V, Golaconda Ramulu H, Drula E, Coutinho PM, and Henrissat B. (2014). The carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res. 2014;42(Database issue):D490-5. DOI:10.1093/nar/gkt1178 |
4. Levasseur A, Drula E, Lombard V, Coutinho PM, and Henrissat B. (2013). Expansion of the enzymatic repertoire of the CAZy database to integrate auxiliary redox enzymes. Biotechnol Biofuels. 2013;6(1):41. DOI:10.1186/1754-6834-6-41 |
5. Lombard V, Bernard T, Rancurel C, Brumer H, Coutinho PM, and Henrissat B. (2010). A hierarchical classification of polysaccharide lyases for glycogenomics. Biochem J. 2010;432(3):437-44. DOI:10.1042/BJ20101185 |
6. Garron ML and Cygler M. (2010). Structural and mechanistic classification of uronic acid-containing polysaccharide lyases. Glycobiology. 2010;20(12):1547-73. DOI:10.1093/glycob/cwq122 |
7. Boraston AB, Bolam DN, Gilbert HJ, and Davies GJ. (2004). Carbohydrate-binding modules: fine-tuning polysaccharide recognition. Biochem J. 2004;382(Pt 3):769-81. DOI:10.1042/BJ20040892 |
8. Shoseyov O, Shani Z, and Levy I. (2006). Carbohydrate binding modules: biochemical properties and novel applications. Microbiol Mol Biol Rev. 2006;70(2):283-95. DOI:10.1128/MMBR.00028-05 |
9. Hashimoto H (2006). Recent structural studies of carbohydrate-binding modules. Cell Mol Life Sci. 2006;63(24):2954-67. DOI:10.1007/s00018-006-6195-3 |
10. Guillén D, Sánchez S, and Rodríguez-Sanoja R. (2010). Carbohydrate-binding domains: multiplicity of biological roles. Appl Microbiol Biotechnol. 2010;85(5):1241-9. DOI:10.1007/s00253-009-2331-y |
11. Gilbert HJ, Knox JP, and Boraston AB. (2013). Advances in understanding the molecular basis of plant cell wall polysaccharide recognition by carbohydrate-binding modules. Curr Opin Struct Biol. 2013;23(5):669-77. DOI:10.1016/j.sbi.2013.05.005 |
12. Lairson LL, Henrissat B, Davies GJ, and Withers SG. (2008). Glycosyltransferases: structures, functions, and mechanisms. Annu Rev Biochem. 2008;77:521-55. DOI:10.1146/annurev.biochem.76.061005.092322 |