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Glycoside Hydrolase Family 129

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Glycoside Hydrolase Family GH129
Clan none
Mechanism retaining
Active site residues not known
CAZy DB link
http://www.cazy.org/GH129.html


Substrate specificities

This family of glycoside hydrolases was established based on the α-N-acetylgalactosaminidase (NagBb) from Bifidobacterium bifidum JCM 1254, which shows slight sequence similarity with GH101 endo-α-N-acetylgalactosaminidases [1]. Before the establishment of this family, it has been predicted as a hypothetical glycoside hydrolase-like (GHL) family GHL1 [2, 3]. NagBb acts more rapidly on GalNAcα1-pNP than Galβ1-3GalNAcα1-pNP, therefore its substrate specificity is quite different from GH101 enzymes (EC 3.2.1.97). This specificity is also different from those of previously known exo-α-N-acetylgalactosaminidases (EC 3.2.1.49) in GH27, GH36 and GH109. As such, NagBb may be appropriately referred to as a exo/endo-α-N-acetylgalactosaminidase.

NagBb most preferably hydrolyzes GalNAcα1-Ser, a minimal structure of Tn antigen on mucin-type glycoproteins, suggesting that NagBb might be involved in degradation of intestinal mucins. The members of GH129 are distributed in several bifidobacterial species such as B. longum subsp. longum, B. longum subsp. infants and B. breve, which are frequently found in intestines of infants.

Kinetics and Mechanism

NagBb is a retaining enzyme. The stereochemistry of hydrolysis has been monitored by normal-phase HPLC using GalNAcα1-pNP as a substrate [1]. GH129 is distantly related to GH101 as well as GH13 α-amylases; members of these latter two families are also classified as retaining enzymes.

Catalytic Residues

Asp435 in NagBb is predicted as catalytic nucleophile by remote homology-based fold recognition using GH13 α-amylase 1 (TVAI) from Thermoactinomyces vulgaris R-47 (PDB code 1JI1) as a template [1]. Asp330 in NagBb may be the so-called "fixer": analogous to the third invariant actve-site residue conserved in GH101 and GH13 enzymes, which is proposed as a transition state stabilizer. The general acid/base residue in GH129 unknown.

Three-dimensional structures

Currently not determined experimentally.

Family Firsts

First stereochemistry determination
NagBb from Bifidobacterium bifidum JCM 1254 by normal-phase HPLC [1].
First catalytic nucleophile identification
Predicted to be Asp435 in NagBb based on homology modelling [1].
First general acid/base residue identification
Not known.
First 3-D structure
None.

References

  1. Kiyohara M, Nakatomi T, Kurihara S, Fushinobu S, Suzuki H, Tanaka T, Shoda S, Kitaoka M, Katayama T, Yamamoto K, and Ashida H. (2012) α-N-acetylgalactosaminidase from infant-associated bifidobacteria belonging to novel glycoside hydrolase family 129 is implicated in alternative mucin degradation pathway. J Biol Chem. 287, 693-700. DOI:10.1074/jbc.M111.277384 | PubMed ID:22090027 | HubMed [Kiyohara2012a]
  2. Naumoff DG (2010) GH101 family of glycoside hydrolases: subfamily structure and evolutionary connections with other families. J Bioinform Comput Biol. 8, 437-51. PubMed ID:20556855 | HubMed [Naumoff2010]
  3. Naumov DG (2011) [GHL1-GHL15: new families of hypothetical glycoside hydrolases]. Mol Biol (Mosk). 45, 1073-83. PubMed ID:22295578 | HubMed [Naumoff2011]
All Medline abstracts: PubMed | HubMed