Skip to main content
Article
Theory and computation show that Asp463 is the catalytic proton donor in human endoplasmic reticulum α-(1→2)-mannosidase I
Carbohydrate Research
  • David C. Cantú, Iowa State University
  • Wim Nerinckx, Ghent University
  • Peter J. Reilly, Iowa State University
Document Type
Article
Publication Date
9-8-2008
DOI
10.1016/j.carres.2008.05.026
Abstract

It has been difficult to identify the proton donor and nucleophilic assistant/base of endoplasmic reticulum α-(1→2)-mannosidase I, a member of glycoside hydrolase Family 47, which cleaves the glycosidic bond between two α-(1→2)-linked mannosyl residues by the inverting mechanism, trimming Man9GlcNAc2 to Man8GlcNAc2 isomer B. Part of the difficulty is caused by the enzyme’s use of a water molecule to transmit the proton that attacks the glycosidic oxygen atom. We earlier used automated docking to conclusively determine that Glu435 in the yeast enzyme (Glu599 in the corresponding human enzyme) is the nucleophilic assistant. The commonly accepted proton donor has been Glu330 in the human enzyme (Glu132 in the yeast enzyme). However, for theoretical reasons this conclusion is untenable. Theory, automated docking of α-d-3S1-mannopyranosyl-(1→2)-α-d-4C1-mannopyranose and water molecules associated with candidate proton donors, and estimation of dissociation constants of the latter have shown that the true proton donor is Asp463 in the human enzyme (Asp275 in the yeast enzyme).

Comments

This is a post-print of an article from Carbohydrate Research, 343, no. 13 (8 September 2008): 2235–2242, doi: 10.1016/j.carres.2008.05.026.

Copyright Owner
Elsevier Ltd.
Language
en
File Format
application/pdf
Citation Information
David C. Cantú, Wim Nerinckx and Peter J. Reilly. "Theory and computation show that Asp463 is the catalytic proton donor in human endoplasmic reticulum α-(1→2)-mannosidase I" Carbohydrate Research Vol. 343 Iss. 13 (2008) p. 2235 - 2242
Available at: http://works.bepress.com/peter_reilly/14/