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Difference between revisions of "Glycoside Hydrolase Family 79"

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* [[Author]]: ^^^Hitomi Ichinose^^^ and ^^^Satoshi Kaneko^^^
* [[Author]]: ^^^Hitomi Ichinose^^^ and ^^^Satoshi Kaneko^^^
* [[Responsible Curator]]:  ^^^Satoshi Kaneko^^^
* [[Responsible Curator]]:  ^^^Satoshi Kaneko^^^

Revision as of 00:03, 9 March 2012

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Glycoside Hydrolase Family GH79
Clan GH-A
Mechanism retaining
Active site residues known
CAZy DB link

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 (E.C. [1], β-4-O-methyl-glucuronidase (E.C. 3.2.1.-) [2], baicalin β-glucuronidase (E.C. [3], heparanase (E.C. 3.2.1.-) [4, 5, 6, 7, 8] and hyaluronidase (E.C. 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 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 the 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 [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 [11].


  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. 49, 1331-41. DOI:10.1093/pcp/pcn108 | PubMed ID:18667448 | HubMed [Eudes2008]
  2. Kuroyama H, Tsutsui N, Hashimoto Y, and Tsumuraya Y. (2001) Purification and characterization of a beta-glucuronidase from Aspergillus niger. Carbohydr Res. 333, 27-39. PubMed ID:11423108 | HubMed [Kuroyama2001]
  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. 275, 27466-72. DOI:10.1074/jbc.M004674200 | PubMed ID:10858442 | HubMed [Sasaki2000]
  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. 5, 793-802. DOI:10.1038/10518 | PubMed ID:10395325 | HubMed [Vlodavsky1999]
  5. Toyoshima M and Nakajima M. (1999) Human heparanase. Purification, characterization, cloning, and expression. J Biol Chem. 274, 24153-60. PubMed ID:10446189 | HubMed [Toyoshima1999]
  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. 261, 183-7. DOI:10.1006/bbrc.1999.0962 | PubMed ID:10405343 | HubMed [Kussie1999]
  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. 5, 803-9. DOI:10.1038/10525 | PubMed ID:10395326 | HubMed [Hulett1999]
  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. 274, 29587-90. PubMed ID:10514423 | HubMed [Fairbanks1999]
  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. 43, 1862-73. DOI:10.1021/bi030203a | PubMed ID:14967027 | HubMed [Nardella2004]
  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. 343, 1191-201. DOI:10.1016/j.carres.2008.03.004 | PubMed ID:18377882 | HubMed [Konishi2008]
  11. Michikawa M, Ichinose H, Momma M, Biely P, Jongkees S, Yoshida M, Kotake T, Tsumuraya Y, Withers S, Fujimoto Z, Kaneko S. Structural and biochemical characterization of glycoside hydrolase family 79 β-glucuronidase from Acidobacterium capsulatum. J. Biol. Chem. in press. PMID=22367201
All Medline abstracts: PubMed | HubMed