کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1389408 | 982877 | 2006 | 13 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Docking studies on glycoside hydrolase Family 47 endoplasmic reticulum α-(1→2)-mannosidase I to elucidate the pathway to the substrate transition state Docking studies on glycoside hydrolase Family 47 endoplasmic reticulum α-(1→2)-mannosidase I to elucidate the pathway to the substrate transition state](/preview/png/1389408.png)
α-(1→2)-Mannosidase I from the endoplasmic reticulum (ERManI), a Family 47 glycoside hydrolase, is a key enzyme in the N-glycan synthesis pathway. Catalytic-domain crystal structures of yeast and human ERMan1s have been determined, the former with a hydrolytic product and the latter without ligands, with the inhibitors 1-deoxymannojirimycin and kifunensine, and with a thiodisaccharide substrate analog. Both inhibitors were bound at the base of the funnel-shaped active site as the unusual 1C4 conformer, while the substrate analog glycon is a 3S1 conformer. In the current study, AutoDock was used to dock α-d-mannopyranosyl-(1→2)-α-d-mannopyranose with its glycon in chair (1C4, 4C1), half-chair (3H2, 3H4, 4H3), skew-boat (OS2, 3S1, 5S1), boat (2,5B, 3,OB, B1,4, B2,5), and envelope (3E, 4E, E3, E4) conformations into the yeast ERManI active site. Both docked energies and forces on docked ligand atoms were calculated to determine how the ligand distorts to the transition state. From these, we can conclude that (1) both 1C4 and OS2 can be the starting conformers; (2) the most likely binding pathway is 1C4 → 3H2 → OS2 → 3,OB → 3S1 → 3E; (3) the transition state is likely to be close to a 3E conformation.
Computed forces in pN on α-d-mannopyranosyl-(1→2)-α-d-mannopyranose exerted by the active site of yeast α-(1→2)-mannosidase.Figure optionsDownload as PowerPoint slide
Journal: Carbohydrate Research - Volume 341, Issue 13, 25 September 2006, Pages 2233–2245