Glycoside Hydrolase Family 79

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• Author: ^^^Hitomi Ichinose^^^ and ^^^Satoshi Kaneko^^^
• Responsible Curator: ^^^Satoshi Kaneko^^^

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Glycoside Hydrolase Family GH79
Clan	GH-A
Mechanism	retaining
Active site residues	known
CAZy DB link
https://www.cazy.org/GH79.html

Substrate specificities

Family GH79 enzymes are found widely distributed in bacteria and eukaryota including fungi, plants, and animals. The characterized activities of this family include β-glucuronidase (EC 3.2.1.31) [1], β-4-O-methyl-glucuronidase (EC 3.2.1.-) [2], baicalin β-glucuronidase (EC 3.2.1.167) [3], heparanase (EC 3.2.1.166) [4, 5, 6, 7, 8] and hyaluronidase (EC 3.2.1.-) [9]. GH79s are involved in the metabolism of proteoglycans, such as heparan sulfate proteoglycan, chondroitin sulfate proteoglycan, and hyaluronan from animals and arabinogalactan-proteins from higher plants.

Some β-glucuronidases have been shown to release both glucuronic acid (GlcA) and 4-O-methyl-GlcA from arabinogalactan proteins [2, 10]. The Aspergillus niger enzyme shows high activity for 4-O-methyl-GlcA residues [2]. Scutellaria baicalensis β-glucuronidase hydrolyzes baicalein 7-O-β-glucuronide, which is a major flavone of S. baicalensis [3]. Heparanase is an endo-β-glucuronidase that degrades the heparan sulfate side chains of heparan sulfate proteoglycans. Heparanases are found in mammals such as human, mouse (Mus musculus), rat (Rattus norvegicus), cattle (Bos indicus), and chicken (Gallus gallus).

Kinetics and Mechanism

GH79 β-glucuronidases are retaining enzymes, as first demonstrated by proton-NMR studies of the hydrolysis of p-nitrophenyl β-glucuronide by a β-glucuronidase from Acidobacterium capsulatum [11].

Catalytic Residues

The catalytic residues were first identified in the A. capsulatum β-glucuronidase as Glu173 (acid/base) and Glu287 (nucleophile) by trapping of the 2-fluoroglucuronyl-enzyme intermediate and site-directed mutagenesis studies [11].

Three-dimensional structures

The three-dimensional structure of A. capsulatum β-glucuronidase solved using X-ray crystallography represented the first structure of an enzyme of GH79 (PDB IDs 3vny, 3vnz, 3vo0) [11]. The catalytic domain of the enzyme is a (β/α)8 TIM-barrel fold as members of clan GH-A.

Family Firsts

First stereochemistry determination

Acidobacterium capsulatum β-glucuronidase by 1H-NMR [11].

First catalytic nucleophile identification

A. capsulatum β-glucuronidase by 2-fluoroglucuroic acid labeling and the mutagenesis study [11].

First general acid/base residue identification

A. capsulatum β-glucuronidase by structural identification and the mutagenesis study [11].

First 3-D structure

A. capsulatum β-glucuronidase (PDB IDs 3vny, 3vnz, 3vo0) [11].

References

1. Eudes A, Mouille G, Thévenin J, Goyallon A, Minic Z, and Jouanin L. (2008). Purification, cloning and functional characterization of an endogenous beta-glucuronidase in Arabidopsis thaliana. Plant Cell Physiol. 2008;49(9):1331-41. DOI:10.1093/pcp/pcn108 |
2. Kuroyama H, Tsutsui N, Hashimoto Y, and Tsumuraya Y. (2001). Purification and characterization of a beta-glucuronidase from Aspergillus niger. Carbohydr Res. 2001;333(1):27-39. DOI:10.1016/s0008-6215(01)00114-8 |
3. Sasaki K, Taura F, Shoyama Y, and Morimoto S. (2000). Molecular characterization of a novel beta-glucuronidase from Scutellaria baicalensis georgi. J Biol Chem. 2000;275(35):27466-72. DOI:10.1074/jbc.M004674200 |
4. Vlodavsky I, Friedmann Y, Elkin M, Aingorn H, Atzmon R, Ishai-Michaeli R, Bitan M, Pappo O, Peretz T, Michal I, Spector L, and Pecker I. (1999). Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nat Med. 1999;5(7):793-802. DOI:10.1038/10518 |
5. Toyoshima M and Nakajima M. (1999). Human heparanase. Purification, characterization, cloning, and expression. J Biol Chem. 1999;274(34):24153-60. DOI:10.1074/jbc.274.34.24153 |
6. Kussie PH, Hulmes JD, Ludwig DL, Patel S, Navarro EC, Seddon AP, Giorgio NA, and Bohlen P. (1999). Cloning and functional expression of a human heparanase gene. Biochem Biophys Res Commun. 1999;261(1):183-7. DOI:10.1006/bbrc.1999.0962 |
7. Hulett MD, Freeman C, Hamdorf BJ, Baker RT, Harris MJ, and Parish CR. (1999). Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis. Nat Med. 1999;5(7):803-9. DOI:10.1038/10525 |
8. Fairbanks MB, Mildner AM, Leone JW, Cavey GS, Mathews WR, Drong RF, Slightom JL, Bienkowski MJ, Smith CW, Bannow CA, and Heinrikson RL. (1999). Processing of the human heparanase precursor and evidence that the active enzyme is a heterodimer. J Biol Chem. 1999;274(42):29587-90. DOI:10.1074/jbc.274.42.29587 |
9. Nardella C, Lahm A, Pallaoro M, Brunetti M, Vannini A, and Steinkühler C. (2004). Mechanism of activation of human heparanase investigated by protein engineering. Biochemistry. 2004;43(7):1862-73. DOI:10.1021/bi030203a |
10. Konishi T, Kotake T, Soraya D, Matsuoka K, Koyama T, Kaneko S, Igarashi K, Samejima M, and Tsumuraya Y. (2008). Properties of family 79 beta-glucuronidases that hydrolyze beta-glucuronosyl and 4-O-methyl-beta-glucuronosyl residues of arabinogalactan-protein. Carbohydr Res. 2008;343(7):1191-201. DOI:10.1016/j.carres.2008.03.004 |
11. Michikawa M, Ichinose H, Momma M, Biely P, Jongkees S, Yoshida M, Kotake T, Tsumuraya Y, Withers SG, Fujimoto Z, and Kaneko S. (2012). Structural and biochemical characterization of glycoside hydrolase family 79 β-glucuronidase from Acidobacterium capsulatum. J Biol Chem. 2012;287(17):14069-77. DOI:10.1074/jbc.M112.346288 |