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Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides
by
Wang, Lai-Xi
, Guerin, Marcelo E.
, Du, Jonathan J.
, Sundberg, Eric J.
, Trastoy, Beatriz
, Cifuente, Javier O.
, Klontz, Erik H.
, Li, Chao
in
631/45/221
/ 631/535/1266
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Bacteroides thetaiotaomicron - chemistry
/ Bacteroides thetaiotaomicron - enzymology
/ Bacteroides thetaiotaomicron - genetics
/ Bacteroides thetaiotaomicron - metabolism
/ Gastrointestinal Microbiome
/ Gene Expression Regulation, Bacterial
/ Glycoside Hydrolases - chemistry
/ Glycoside Hydrolases - genetics
/ Glycoside Hydrolases - metabolism
/ Humanities and Social Sciences
/ Humans
/ Mannose - chemistry
/ Mannose - metabolism
/ multidisciplinary
/ Polysaccharides - chemistry
/ Polysaccharides - metabolism
/ Science
/ Science (multidisciplinary)
/ Substrate Specificity
2020
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Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides
by
Wang, Lai-Xi
, Guerin, Marcelo E.
, Du, Jonathan J.
, Sundberg, Eric J.
, Trastoy, Beatriz
, Cifuente, Javier O.
, Klontz, Erik H.
, Li, Chao
in
631/45/221
/ 631/535/1266
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Bacteroides thetaiotaomicron - chemistry
/ Bacteroides thetaiotaomicron - enzymology
/ Bacteroides thetaiotaomicron - genetics
/ Bacteroides thetaiotaomicron - metabolism
/ Gastrointestinal Microbiome
/ Gene Expression Regulation, Bacterial
/ Glycoside Hydrolases - chemistry
/ Glycoside Hydrolases - genetics
/ Glycoside Hydrolases - metabolism
/ Humanities and Social Sciences
/ Humans
/ Mannose - chemistry
/ Mannose - metabolism
/ multidisciplinary
/ Polysaccharides - chemistry
/ Polysaccharides - metabolism
/ Science
/ Science (multidisciplinary)
/ Substrate Specificity
2020
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Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides
by
Wang, Lai-Xi
, Guerin, Marcelo E.
, Du, Jonathan J.
, Sundberg, Eric J.
, Trastoy, Beatriz
, Cifuente, Javier O.
, Klontz, Erik H.
, Li, Chao
in
631/45/221
/ 631/535/1266
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Bacteroides thetaiotaomicron - chemistry
/ Bacteroides thetaiotaomicron - enzymology
/ Bacteroides thetaiotaomicron - genetics
/ Bacteroides thetaiotaomicron - metabolism
/ Gastrointestinal Microbiome
/ Gene Expression Regulation, Bacterial
/ Glycoside Hydrolases - chemistry
/ Glycoside Hydrolases - genetics
/ Glycoside Hydrolases - metabolism
/ Humanities and Social Sciences
/ Humans
/ Mannose - chemistry
/ Mannose - metabolism
/ multidisciplinary
/ Polysaccharides - chemistry
/ Polysaccharides - metabolism
/ Science
/ Science (multidisciplinary)
/ Substrate Specificity
2020
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Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides
Journal Article
Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides
2020
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Overview
The human gut microbiota plays a central role not only in regulating the metabolism of nutrients but also promoting immune homeostasis, immune responses and protection against pathogen colonization. The genome of the Gram-negative symbiont
Bacteroides thetaiotaomicron
, a dominant member of the human intestinal microbiota, encodes polysaccharide utilization loci PULs, the apparatus required to orchestrate the degradation of a specific glycan. EndoBT-3987 is a key endo-β-
N
-acetylglucosaminidase (ENGase) that initiates the degradation/processing of mammalian high-mannose-type (HM-type)
N
-glycans in the intestine. Here, we provide structural snapshots of EndoBT-3987, including the unliganded form, the EndoBT-3987-Man
9
GlcNAc
2
Asn substrate complex, and two EndoBT-3987-Man
9
GlcNAc and EndoBT-3987-Man
5
GlcNAc product complexes. In combination with alanine scanning mutagenesis and activity measurements we unveil the molecular mechanism of HM-type recognition and specificity for EndoBT-3987 and an important group of the GH18 ENGases, including EndoH, an enzyme extensively used in biotechnology, and for which the mechanism of substrate recognition was largely unknown.
Human gut bacteria depolymerize glycans into their sugar components, which otherwise cannot be processed by their host. Here, the authors characterise the endo-β-
N
-acetylglucosaminidase EndoBT-3987 from the Gram-negative symbiont
Bacteroides thetaiotaomicron
and present the crystal structures of ligand-free EndoBT-3987, a substrate bound complex and product complexes.
Publisher
Nature Publishing Group UK,Nature Portfolio
Subject
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Bacteroides thetaiotaomicron - chemistry
/ Bacteroides thetaiotaomicron - enzymology
/ Bacteroides thetaiotaomicron - genetics
/ Bacteroides thetaiotaomicron - metabolism
/ Gene Expression Regulation, Bacterial
/ Glycoside Hydrolases - chemistry
/ Glycoside Hydrolases - genetics
/ Glycoside Hydrolases - metabolism
/ Humanities and Social Sciences
/ Humans
/ Polysaccharides - metabolism
/ Science
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