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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2018
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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. |
format | Online Article Text |
id | pubmed-5930347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
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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