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Bacteroides thetaiotaomicron generates diverse α-mannosidase activities through subtle evolution of a distal substrate-binding motif

A dominant human gut microbe, the well studied symbiont Bacteroides thetaiotaomicron (Bt), is a glyco-specialist that harbors a large repertoire of genes devoted to carbohydrate processing. Despite strong similarities among them, many of the encoded enzymes have evolved distinct substrate specificit...

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Autores principales: Thompson, Andrew J., Spears, Richard J., Zhu, Yanping, Suits, Michael D. L., Williams, Spencer J., Gilbert, Harry J., Davies, Gideon J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930347/
https://www.ncbi.nlm.nih.gov/pubmed/29717710
http://dx.doi.org/10.1107/S2059798318002942
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author Thompson, Andrew J.
Spears, Richard J.
Zhu, Yanping
Suits, Michael D. L.
Williams, Spencer J.
Gilbert, Harry J.
Davies, Gideon J.
author_facet Thompson, Andrew J.
Spears, Richard J.
Zhu, Yanping
Suits, Michael D. L.
Williams, Spencer J.
Gilbert, Harry J.
Davies, Gideon J.
author_sort Thompson, Andrew J.
collection PubMed
description A dominant human gut microbe, the well studied symbiont Bacteroides thetaiotaomicron (Bt), is a glyco-specialist that harbors a large repertoire of genes devoted to carbohydrate processing. Despite strong similarities among them, many of the encoded enzymes have evolved distinct substrate specificities, and through the clustering of cognate genes within operons termed polysaccharide-utilization loci (PULs) enable the fulfilment of complex biological roles. Structural analyses of two glycoside hydrolase family 92 α-mannosidases, BT3130 and BT3965, together with mechanistically relevant complexes at 1.8–2.5 Å resolution reveal conservation of the global enzyme fold and core catalytic apparatus despite different linkage specificities. Structure comparison shows that Bt differentiates the activity of these enzymes through evolution of a highly variable substrate-binding region immediately adjacent to the active site. These observations unveil a genetic/biochemical mechanism through which polysaccharide-processing bacteria can evolve new and specific biochemical activities from otherwise highly similar gene products.
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spelling pubmed-59303472018-05-11 Bacteroides thetaiotaomicron generates diverse α-mannosidase activities through subtle evolution of a distal substrate-binding motif Thompson, Andrew J. Spears, Richard J. Zhu, Yanping Suits, Michael D. L. Williams, Spencer J. Gilbert, Harry J. Davies, Gideon J. Acta Crystallogr D Struct Biol Research Papers A dominant human gut microbe, the well studied symbiont Bacteroides thetaiotaomicron (Bt), is a glyco-specialist that harbors a large repertoire of genes devoted to carbohydrate processing. Despite strong similarities among them, many of the encoded enzymes have evolved distinct substrate specificities, and through the clustering of cognate genes within operons termed polysaccharide-utilization loci (PULs) enable the fulfilment of complex biological roles. Structural analyses of two glycoside hydrolase family 92 α-mannosidases, BT3130 and BT3965, together with mechanistically relevant complexes at 1.8–2.5 Å resolution reveal conservation of the global enzyme fold and core catalytic apparatus despite different linkage specificities. Structure comparison shows that Bt differentiates the activity of these enzymes through evolution of a highly variable substrate-binding region immediately adjacent to the active site. These observations unveil a genetic/biochemical mechanism through which polysaccharide-processing bacteria can evolve new and specific biochemical activities from otherwise highly similar gene products. International Union of Crystallography 2018-04-24 /pmc/articles/PMC5930347/ /pubmed/29717710 http://dx.doi.org/10.1107/S2059798318002942 Text en © Thompson et al. 2018 http://creativecommons.org/licenses/by/2.0/uk/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/2.0/uk/
spellingShingle Research Papers
Thompson, Andrew J.
Spears, Richard J.
Zhu, Yanping
Suits, Michael D. L.
Williams, Spencer J.
Gilbert, Harry J.
Davies, Gideon J.
Bacteroides thetaiotaomicron generates diverse α-mannosidase activities through subtle evolution of a distal substrate-binding motif
title Bacteroides thetaiotaomicron generates diverse α-mannosidase activities through subtle evolution of a distal substrate-binding motif
title_full Bacteroides thetaiotaomicron generates diverse α-mannosidase activities through subtle evolution of a distal substrate-binding motif
title_fullStr Bacteroides thetaiotaomicron generates diverse α-mannosidase activities through subtle evolution of a distal substrate-binding motif
title_full_unstemmed Bacteroides thetaiotaomicron generates diverse α-mannosidase activities through subtle evolution of a distal substrate-binding motif
title_short Bacteroides thetaiotaomicron generates diverse α-mannosidase activities through subtle evolution of a distal substrate-binding motif
title_sort bacteroides thetaiotaomicron generates diverse α-mannosidase activities through subtle evolution of a distal substrate-binding motif
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930347/
https://www.ncbi.nlm.nih.gov/pubmed/29717710
http://dx.doi.org/10.1107/S2059798318002942
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