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PDBsum entry 6hmh
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PDB id:
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Hydrolase
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Title:
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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
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Structure:
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Glycosyl hydrolase family 71. Chain: a. Engineered: yes
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Source:
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Bacteroides xylanisolvens xb1a. Organism_taxid: 657309. Gene: bxy_34140. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008
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Resolution:
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1.03Å
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R-factor:
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0.125
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R-free:
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0.139
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Authors:
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L.F.Sobala,D.Lu,S.Zhu,G.Bernardo-Seisdedos,O.Millet,Y.Zhang, M.Sollogoub,J.Jimenez-Barbero,G.J.Davies
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Key ref:
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D.Lu
et al.
(2018).
From 1,4-Disaccharide to 1,3-Glycosyl Carbasugar: Synthesis of a Bespoke Inhibitor of Family GH99 Endo-α-mannosidase.
Org Lett,
20,
7488-7492.
PubMed id:
DOI:
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Date:
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12-Sep-18
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Release date:
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26-Sep-18
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PROCHECK
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Headers
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References
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D6D1V7
(D6D1V7_9BACE) -
Glycosyl hydrolase family 71 from Bacteroides xylanisolvens XB1A
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Seq:
Struc:
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380 a.a.
341 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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DOI no:
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Org Lett
20:7488-7492
(2018)
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PubMed id:
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From 1,4-Disaccharide to 1,3-Glycosyl Carbasugar: Synthesis of a Bespoke Inhibitor of Family GH99 Endo-α-mannosidase.
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D.Lu,
S.Zhu,
L.F.Sobala,
G.Bernardo-Seisdedos,
O.Millet,
Y.Zhang,
J.Jiménez-Barbero,
G.J.Davies,
M.Sollogoub.
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ABSTRACT
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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.
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