Informace o publikaci
Docking study of the potential glycosyltransferase inhibitors
| Autoři | |
|---|---|
| Rok publikování | 2009 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Glycosyltransferases are involved in the biosynthesis of glycans, which play an important role in many biological events. The N-acetylglucosaminyltransferase I catalyzes the transfer of a GlcNAc residue from the donor UDP-GlcNAc to the acceptor, which is the C2-hydroxyl group of a mannose residue in the trimannosyl core of the Man5GlcNAc2-Asn-X oligosaccharide. Previous molecular modeling studies determined the structure of a transition state (TS) for the enzymatic reaction catalyzed by GnT-I. The proposed scaffold uses the alkylthio and phosphonate groups linked to the anomeric centre of five-member ring to mimic the arrangement of GlcNAc, UDP and acceptor in TS. The conformational properties of the analogue were investigated by DFT(B3LYP) methods using Schrödinger software packages. a- and b- anomers of the stable conformer were docked into crystal structure of GnT-I (PDB code 1FOA) using the Glide software. The binding energy was computed using the Liaison software. The computed energies were compared with the binding energy calculated for the natural substrate UDP-GlcNAc. |