Document Type

Article

Publication Date

2-5-2007

Journal or Book Title

Carbohydrate Research

Volume

342

Issue

2

First Page

163

Last Page

169

DOI

10.1016/j.carres.2006.11.012

Abstract

The automated docking program AutoDock was used to dock all 38 characteristic β-d-mannopyranose ring conformers into the active site of the yeast endoplasmic reticulum α-(1→2)-mannosidase I, a Family 47 glycoside hydrolase that converts Man9GlcNAc2 to Man8GlcNAc2. The subject of this work is to establish the conformational pathway that allows the cleaved glycon product to leave the enzyme active site and eventually reach the ground-state conformation. Twelve of the 38 conformers optimally dock in the active site where the inhibitors 1-deoxymannonojirimycin and kifunensine are found in enzyme crystal structures. A further 23 optimally dock in a second site on the side of the active-site well, while three dock outside the active-site cavity. It appears, through analysis of the internal energies of different ring conformations, of intermolecular energies between the ligands and enzyme, and of forces exerted on the ligands by the enzyme, that β-d-mannopyranose follows the path 3E1C41H2B2,5 before being expelled by the enzyme. The highly conserved second site that strongly binds β-d-mannopyranose-4C1 may exist to prevent competitive inhibition by the product, and is worthy of further investigation.

Comments

This is a post-print of an article from Carbohydrate Research, 342, no. 2 (5 February 2007): 163–169, doi: 10.1016/j.carres.2006.11.012.

Copyright Owner

Elsevier Ltd.

Language

en

File Format

application/pdf

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