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Difference between revisions of "Glycoside Hydrolase Family 37"

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* [[Author]]: ^^^Tracey Gloster^^^
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* [[Author]]: ^^^Tracey Gloster^^^, ^^^Cecelia Garcia^^^
 
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* [[Responsible Curator]]:  ^^^Gideon Davies^^^
 
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== Substrate specificities ==
 
== Substrate specificities ==
GH37 [[glycoside hydrolases]] have been shown, to date, to hydrolyse only the disaccharide trehalose (α-D-glucopyranosyl-(1→1)-α-D-glucopyranoside) into two molecules of D-glucose (EC [{{EClink}}3.2.1.28 3.2.1.28]).
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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 [{{EClink}}3.2.1.28 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 <cite>DEnfert1999</cite>.
  
 
== Kinetics and Mechanism ==
 
== Kinetics and Mechanism ==
A trehalase from flesh fly was shown to hydrolyse with [[inverting|inversion]] of anomeric stereochemistry using <sup>18</sup>O-labelled water <cite>Clifford1980</cite>. The structural solution of the trehalase from ''Escherichia coli'' also demonstrates the active site catalytic residues are in a position consistent with an [[inverting]] mechanism <cite>Gibson2007</cite>.
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GH37 trehalases follow an [[inverting]] mechanism. This was first demonstrated through incubation of GH37 trehalases obtained from ''S. barbata'', the flesh fly, with <sup>18</sup>O-labelled water and observing its incorporation primarily into the beta-epimer <cite>Clifford1980</cite>. 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 <cite>Gibson2007</cite>.
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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 <cite>DEnfert1999 Alblova2017 Alblova2019</cite>.  
  
 
== Catalytic Residues ==
 
== Catalytic Residues ==
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== References ==
 
== References ==
 
<biblio>
 
<biblio>
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#DEnfert1999 pmid=10320571
 
#Clifford1980 pmid=7341233
 
#Clifford1980 pmid=7341233
 
#Gibson2007 pmid=17455176
 
#Gibson2007 pmid=17455176
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#Alblova2017 pmid=29087344
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#Alblova2019 pmid=30628830
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#Cardona2009 pmid=19123216
 
#Cardona2009 pmid=19123216
 
#Cardona2010 pmid=20461849  
 
#Cardona2010 pmid=20461849  

Revision as of 14:19, 8 September 2021

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Glycoside Hydrolase Family GH37
Clan GH-G
Mechanism Inverting
Active site residues Inferred
CAZy DB link
http://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 | PubMed ID:10320571 [DEnfert1999]
  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 | PubMed ID:7341233 [Clifford1980]
  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 | PubMed ID:17455176 [Gibson2007]
  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 | PubMed ID:29087344 [Alblova2017]
  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 | PubMed ID:30628830 [Alblova2019]
  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 | PubMed ID:19123216 [Cardona2009]
  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 | PubMed ID:20461849 [Cardona2010]

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