Document Type

Article

Publication Date

9-25-2012

Journal or Book Title

Carbohydrate Research

Volume

341

Issue

15

First Page

2233

Last Page

2245

DOI

10.1016/j.carres.2006.05.011

Abstract

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 andOS2 can be the starting conformers; (2) the most likely binding pathway is1C43H2OS23,OB3S13E; (3) the transition state is likely to be close to a 3E conformation.

Comments

This is a post-print of an article from Carbohydrate Research, 341, no. 15 (25 September 2007): 2233–2245, doi: 10.1016/j.carres.2006.05.011.

Copyright Owner

Elsevier Ltd.

Language

en

File Format

application/pdf

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