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Article
The fate of β-d-mannopyranose after its formation by endoplasmic reticulum α-(1→2)-mannosidase I catalysis
Carbohydrate Research
  • Chandrika Mulakala, Iowa State University
  • Wim Nerinckx, Ghent University
  • Peter J. Reilly, Iowa State University
Document Type
Article
Publication Date
2-5-2007
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 3E→1C4→1H2→B2,5 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
Date Available
November 19, 2012
File Format
application/pdf
Citation Information
Chandrika Mulakala, Wim Nerinckx and Peter J. Reilly. "The fate of β-d-mannopyranose after its formation by endoplasmic reticulum α-(1→2)-mannosidase I catalysis" Carbohydrate Research Vol. 342 Iss. 2 (2007) p. 163 - 169
Available at: http://works.bepress.com/peter_reilly/6/