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PKa cycling of the general acid/base in glycoside hydrolase families 33 and 34

Journal Article


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Abstract


  • Glycoside hydrolase families 33 and 34 catalyse the hydrolysis of terminal sialic acid residues from sialyl oligosaccharides and glycoconjugates with a net retention of the stereochemistry at the anomeric centre. It is generally believed that the conserved aspartic acid in the active site functions as a general acid to protonate the hydroxyl group of the departing aglycone during glycosylation, and then as a general base to facilitate the nucleophilic attack of the water molecule on the intermediate state during the deglycosylation reaction. The dual role of the general acid/base places specific demands upon its protonation state, and thus pKa values. However, it is not fully understood how this catalytic residue can achieve such pKa cycling during catalysis. We present both MM and combined QM/MM simulations to characterise the pKa values of the proposed catalytic general acid/base in the glycoside hydrolase families 33 and 34. Collectively, our study suggests that the binding of anionic substrates and the local solvation properties along with the neutralisation of the nearby glutamic acid upon glycosylation modulate the electrostatic environment around the general acid/base to achieve its proper protonation states.

Authors


  •   Yu, Haibo
  •   Griffiths, Thomas M. (external author)

Publication Date


  • 2014

Citation


  • Yu, H. & Griffiths, T. M. (2014). PKa cycling of the general acid/base in glycoside hydrolase families 33 and 34. Physical Chemistry Chemical Physics, 16 (12), 5785-5792.

Scopus Eid


  • 2-s2.0-84894822887

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2563&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/1545

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 5785

End Page


  • 5792

Volume


  • 16

Issue


  • 12

Place Of Publication


  • United Kingdom

Abstract


  • Glycoside hydrolase families 33 and 34 catalyse the hydrolysis of terminal sialic acid residues from sialyl oligosaccharides and glycoconjugates with a net retention of the stereochemistry at the anomeric centre. It is generally believed that the conserved aspartic acid in the active site functions as a general acid to protonate the hydroxyl group of the departing aglycone during glycosylation, and then as a general base to facilitate the nucleophilic attack of the water molecule on the intermediate state during the deglycosylation reaction. The dual role of the general acid/base places specific demands upon its protonation state, and thus pKa values. However, it is not fully understood how this catalytic residue can achieve such pKa cycling during catalysis. We present both MM and combined QM/MM simulations to characterise the pKa values of the proposed catalytic general acid/base in the glycoside hydrolase families 33 and 34. Collectively, our study suggests that the binding of anionic substrates and the local solvation properties along with the neutralisation of the nearby glutamic acid upon glycosylation modulate the electrostatic environment around the general acid/base to achieve its proper protonation states.

Authors


  •   Yu, Haibo
  •   Griffiths, Thomas M. (external author)

Publication Date


  • 2014

Citation


  • Yu, H. & Griffiths, T. M. (2014). PKa cycling of the general acid/base in glycoside hydrolase families 33 and 34. Physical Chemistry Chemical Physics, 16 (12), 5785-5792.

Scopus Eid


  • 2-s2.0-84894822887

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2563&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/1545

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 5785

End Page


  • 5792

Volume


  • 16

Issue


  • 12

Place Of Publication


  • United Kingdom