ISSN:
0947-6539
Keywords:
ab initio calculations
;
enzymatic catalysis
;
enzyme models
;
mechanistic studies
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Ab initio quantum mechanical model calculations were used in studying the acylation and deacylation steps of the catalytic mechanism of aspartylglucosaminidase (AGA). AGA catalyses the hydrolysis of an amide linkage between oligosaccharide and asparagine by utilising an N-terminal threonine as a catalytic amino acid. Results are reported for the model enzyme reaction at the MP2/6-31+G*//HF/6-31 + G* + ΔZPE level. Contribution of aqueous solvation to the relative energies was estimated by using the continuum solvation model of Tomasi. The serine protease-like catalytic mechanism was found to be feasible for AGA. The protonated α-amino group of the substrate of AGA was suggested to enhance the catalysis by stabilising the anionic oxygen of the substrate, which is formed in the reaction, and by lowering the pKa of the nucleophilic oxygen of the N-terminal threonine. Finally, the similarities in the catalytic mechanisms of AGA and other amidohydrolases were discussed.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chem.19960021212
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