Enzyme molecular mechanis m of O-GlcNAcase by small molecule inhibitors: A qua ntum mechanical a pproach

O-Glycoprotein ۲-acetamino-۲-deoxy-ȕ- D-glucopyranosidase (O-GlcNAcase ) is a mem ber of the glycoside hydrolases fami ly that hydrolyzes O-GlcNAc residues. O-Glc NAcase catalyzed reacti on takes p lace through a two step mechan ism, Figure ۱, formi ng an oxa zoline interm ediate is a s ubstrate-assisted catalytic process, where the ۲ -acetomide group is activated by an aspartate residue while departure o f the aglyc on leaving group is assisted by mea ns of proton transfer fro m a differe nt protonated aspartate residue [۱, ۲]. In this study, we have used quant um mechanical calculations for studying the catalytic mechanism used by O-GlcN Acase involv ing substrate-assisted c atalysis.

کلیدواژه ها:

O-GlcNAc ، Enzy me inhibitor ، Molecular mechanism ، QM calcu lations