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Chemical and Biological Engineering Publications

GH47

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Full-Text Articles in Biomedical Engineering and Bioengineering

Docking Studies On Glycoside Hydrolase Family 47 Endoplasmic Reticulum Α-(1→2)-Mannosidase I To Elucidate The Pathway To The Substrate Transition State, Chandrika Mulakala, Wim Nerinckx, Peter J. Reilly Sep 2012

Docking Studies On Glycoside Hydrolase Family 47 Endoplasmic Reticulum Α-(1→2)-Mannosidase I To Elucidate The Pathway To The Substrate Transition State, Chandrika Mulakala, Wim Nerinckx, Peter J. Reilly

Chemical and Biological Engineering Publications

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 ...


Theory And Computation Show That Asp463 Is The Catalytic Proton Donor In Human Endoplasmic Reticulum Α-(1→2)-Mannosidase I, David C. Cantú, Wim Nerinckx, Peter J. Reilly Sep 2008

Theory And Computation Show That Asp463 Is The Catalytic Proton Donor In Human Endoplasmic Reticulum Α-(1→2)-Mannosidase I, David C. Cantú, Wim Nerinckx, Peter J. Reilly

Chemical and Biological Engineering Publications

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 ...


The Fate Of Β-D-Mannopyranose After Its Formation By Endoplasmic Reticulum Α-(1→2)-Mannosidase I Catalysis, Chandrika Mulakala, Wim Nerinckx, Peter J. Reilly Feb 2007

The Fate Of Β-D-Mannopyranose After Its Formation By Endoplasmic Reticulum Α-(1→2)-Mannosidase I Catalysis, Chandrika Mulakala, Wim Nerinckx, Peter J. Reilly

Chemical and Biological Engineering Publications

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 ...