Glycoside Hydrolase Family 37

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: ^^^Tracey Gloster^^^, ^^^Cecelia Garcia^^^
• Responsible Curator: ^^^Gideon Davies^^^

---

Glycoside Hydrolase Family GH37
Clan	GH-G
Mechanism	Inverting
Active site residues	Inferred
CAZy DB link
https://www.cazy.org/GH37.html

Substrate specificities

To date, GH37 glycoside hydrolases have been shown to hydrolyze the α-1,1 bound trehalose (α-D-glucopyranosyl-(1→1)-α-D-glucopyranoside) into two molecules of D-glucose (EC 3.2.1.28). GH37 enzymes are further classified by their optimal pH; neutral or acidic, and also by their cellular localization; soluble or membrane bound [1].

Kinetics and Mechanism

GH37 trehalases follow an inverting mechanism. This was first demonstrated through incubation of GH37 trehalases obtained from S. barbata, the flesh fly, with ¹⁸O-labelled water and observing its incorporation primarily into the beta-epimer [2]. This was further supported by the solved structure of E. coli Tre37A which demonstrated that the proposed catalytic residues were in a position consistent with an inverting mechanism [3].

Several fungal neutral trehalases; S. cerevisiae, A. nidulans, N. crassa, and C. albicans, show evidence of activation by calcium ion binding and cAMP-dependent phosphorylation [1, 4, 5].

Catalytic Residues

The catalytic residues have not been demonstrated unequivocally, but structural determination of the trehalase from Escherichia coli in complex with inhibitors in the active site implicate an aspartate residue (Asp312 in E. coli) as the catalytic general acid and a glutamate residue (Glu496 in E. coli) as the catalytic general base [3].

Three-dimensional structures

The only structural representative from GH37 to date is the trehalase from Escherichia coli, which was solved using X-ray crystallography [3]. The structure revealed a (α/α)₆ barrel fold, similar to other α-toroidal glycosidases such as those in families GH94, GH15 and GH65. GH37 falls into clan GH-G. Structures have been solved with the inhibitors validoxylamine A, 1-thiatrehazolin and casuarine analogues [3, 6, 7].

Family Firsts

First sterochemistry determination

The inversion of stereochemistry for a trehalase from the flesh fly Sarcophaga barbata was first demonstrated by Clifford in 1980 [2].

First general acid identification

Predicted from structure determination [3], but not shown unequivocally.

First general base identification

Predicted from structure determination [3], but not shown unequivocally.

First 3-D structure

The GH37 trehalase from Escherichia coli was solved by X-ray crystallography [3].

References

1. d'Enfert C, Bonini BM, Zapella PD, Fontaine T, da Silva AM, and Terenzi HF. (1999). Neutral trehalases catalyse intracellular trehalose breakdown in the filamentous fungi Aspergillus nidulans and Neurospora crassa. Mol Microbiol. 1999;32(3):471-83. DOI:10.1046/j.1365-2958.1999.01327.x |
2. Clifford KH (1980). Stereochemistry of the hydrolysis of trehalose by the enzyme trehalase prepared from the flesh fly Sarcophaga barbata. Eur J Biochem. 1980;106(1):337-40. DOI:10.1111/j.1432-1033.1980.tb06028.x |
3. Gibson RP, Gloster TM, Roberts S, Warren RA, Storch de Gracia I, García A, Chiara JL, and Davies GJ. (2007). Molecular basis for trehalase inhibition revealed by the structure of trehalase in complex with potent inhibitors. Angew Chem Int Ed Engl. 2007;46(22):4115-9. DOI:10.1002/anie.200604825 |
4. Alblova M, Smidova A, Docekal V, Vesely J, Herman P, Obsilova V, and Obsil T. (2017). Molecular basis of the 14-3-3 protein-dependent activation of yeast neutral trehalase Nth1. Proc Natl Acad Sci U S A. 2017;114(46):E9811-E9820. DOI:10.1073/pnas.1714491114 |
5. Alblova M, Smidova A, Kalabova D, Lentini Santo D, Obsil T, and Obsilova V. (2019). Allosteric activation of yeast enzyme neutral trehalase by calcium and 14-3-3 protein. Physiol Res. 2019;68(2):147-160. DOI:10.33549/physiolres.933950 |
6. Cardona F, Parmeggiani C, Faggi E, Bonaccini C, Gratteri P, Sim L, Gloster TM, Roberts S, Davies GJ, Rose DR, and Goti A. (2009). Total syntheses of casuarine and its 6-O-alpha-glucoside: complementary inhibition towards glycoside hydrolases of the GH31 and GH37 families. Chemistry. 2009;15(7):1627-36. DOI:10.1002/chem.200801578 |
7. Cardona F, Goti A, Parmeggiani C, Parenti P, Forcella M, Fusi P, Cipolla L, Roberts SM, Davies GJ, and Gloster TM. (2010). Casuarine-6-O-alpha-D-glucoside and its analogues are tight binding inhibitors of insect and bacterial trehalases. Chem Commun (Camb). 2010;46(15):2629-31. DOI:10.1039/b926600c |