Glycoside Hydrolase Family 136

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• Author: ^^^Chihaya Yamada^^^
• Responsible Curator: ^^^Shinya Fushinobu^^^

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Glycoside Hydrolase Family GH136
Clan	GH-N
Mechanism	retaining
Active site residues	known
CAZy DB link
https://www.cazy.org/GH136.html

Substrate specificities

This family of glycoside hydrolases contains lacto-N-biosidase, as demonstrated for LnbX from Bifidobacterium longum JCM 1217 [1]. LnbX liberates Galβ1-3GlcNAc(lacto-N-biose I, LNB) and lactose from lacto-N-tetraose, the main component of human milk oligosaccharides. It hydrolyzed the linkage GlcNAcβ1-3Gal in lacto-N-hexaose, lacto-N-fucopentaose I, and sialyllacto-N-tetraose a of human milk oligosaccharides as substrate of LnbX in the GH136. In addition, LnbX liberates Galβ1-3GalNAc (GNB) from the sugar chains of globo- and ganglio-series glycosphingolipids [2].

GH136 lacto-N-biosidase required neighboring chaperon gene for folding. Rarely, chaperone-like gene fused to lacto-N-biosidase gene in case of ErGH136_I and ErGH136_IIfrom Eubacterium ramulus [3].

Kinetics and Mechanism

LnbXc hydrolyzes the glycosidic linkage via a retaining mechanism involving a Grotthuss proton relay.

Catalytic Residues

The nucleophile is Asp418. The catalytic acid/base is Asp411 via water molecule.

Three-dimensional structures

Figure 1: Overall structure of LnbXc with LNB (cyan) and two Ca2+ ions (orange).

The X-ray crystal structure of the catalytic domain, LnbXc(31-625) revealed a right-handed β helix fold that is usually shared by polysaccharide active enzymes. Three forms, ligand free (2.36 Å resolution), LNB complex (1.82 Å), and GNB complex (2.70 Å) were determined.

Family Firsts

First stereochemistry determination

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First catalytic nucleophile identification

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First general acid/base residue identification

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First 3-D structure

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References

1. Sakurama H, Kiyohara M, Wada J, Honda Y, Yamaguchi M, Fukiya S, Yokota A, Ashida H, Kumagai H, Kitaoka M, Yamamoto K, and Katayama T. (2013). Lacto-N-biosidase encoded by a novel gene of Bifidobacterium longum subspecies longum shows unique substrate specificity and requires a designated chaperone for its active expression. J Biol Chem. 2013;288(35):25194-25206. DOI:10.1074/jbc.M113.484733 |
2. Gotoh A, Katoh T, Sugiyama Y, Kurihara S, Honda Y, Sakurama H, Kambe T, Ashida H, Kitaoka M, Yamamoto K, and Katayama T. (2015). Novel substrate specificities of two lacto-N-biosidases towards β-linked galacto-N-biose-containing oligosaccharides of globo H, Gb5, and GA1. Carbohydr Res. 2015;408:18-24. DOI:10.1016/j.carres.2015.03.005 |
3. Pichler MJ, Yamada C, Shuoker B, Alvarez-Silva C, Gotoh A, Leth ML, Schoof E, Katoh T, Sakanaka M, Katayama T, Jin C, Karlsson NG, Arumugam M, Fushinobu S, and Abou Hachem M. (2020). Butyrate producing colonic Clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways. Nat Commun. 2020;11(1):3285. DOI:10.1038/s41467-020-17075-x |
4. Yamada C, Gotoh A, Sakanaka M, Hattie M, Stubbs KA, Katayama-Ikegami A, Hirose J, Kurihara S, Arakawa T, Kitaoka M, Okuda S, Katayama T, and Fushinobu S. (2017). Molecular Insight into Evolution of Symbiosis between Breast-Fed Infants and a Member of the Human Gut Microbiome Bifidobacterium longum. Cell Chem Biol. 2017;24(4):515-524.e5. DOI:10.1016/j.chembiol.2017.03.012 |