6HMH

Structure of the GH99 endo-alpha-mannanase from Bacteroides xylanisolvens in complex with alpha-Glc-1,3-(1,2-anhydro-carba-glucosamine) and alpha-1,2-mannobiose

Summary for 6HMH

• Entry DOI: 10.2210/pdb6hmh/pdb
• Related PRD ID: PRD_900111
• Descriptor: Glycosyl hydrolase family 71, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose, ACETATE ION, ... (6 entities in total)
• Functional Keywords: hydrolase
• Biological source: Bacteroides xylanisolvens XB1A
• Total number of polymer chains: 1
• Total formula weight: 44674.27

Authors

Sobala, L.F.,Lu, D.,Zhu, S.,Bernardo-Seisdedos, G.,Millet, O.,Zhang, Y.,Sollogoub, M.,Jimenez-Barbero, J.,Davies, G.J. (deposition date: 2018-09-12, release date: 2018-09-26, Last modification date: 2024-01-24)

Primary citation

Lu, D.,Zhu, S.,Sobala, L.F.,Bernardo-Seisdedos, G.,Millet, O.,Zhang, Y.,Jimenez-Barbero, J.,Davies, G.J.,Sollogoub, M.
From 1,4-Disaccharide to 1,3-Glycosyl Carbasugar: Synthesis of a Bespoke Inhibitor of Family GH99 Endo-alpha-mannosidase.
Org.Lett., 20:7488-7492, 2018

PubMed Abstract: Understanding the enzyme reaction mechanism can lead to the design of enzyme inhibitors. A Claisen rearrangement was used to allow conversion of an α-1,4-disaccharide into an α-1,3-linked glycosyl carbasugar to target the endo-α-mannosidase from the GH99 glycosidase family, which, unusually, is believed to act through a 1,2-anhydrosugar "epoxide" intermediate. Using NMR and X-ray crystallography, it is shown that glucosyl carbasugar α-aziridines can act as reasonably potent endo-α-mannosidase inhibitors, likely by virtue of their shape mimicry and the interactions of the aziridine nitrogen with the conserved catalytic acid/base of the enzyme active site.

PubMed: 30427198
DOI: 10.1021/acs.orglett.8b03260

Experimental method

X-RAY DIFFRACTION (1.03 Å)