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The catalytic domains of Streptococcus mutans glucosyltransferases: a structural analysis
Streptococcus mutans, found in the human oral cavity, is a significant contributor to the pathogenesis of dental caries. This bacterium expresses three genetically distinct types of glucosyltransferases named GtfB (GTF-I), GtfC (GTF-SI) and GtfD (GTF-S) that play critical roles in the development of...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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International Union of Crystallography
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10167749/ https://www.ncbi.nlm.nih.gov/pubmed/37158310 http://dx.doi.org/10.1107/S2053230X23003199 |
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author | Schormann, Norbert Patel, Manisha Thannickal, Luke Purushotham, Sangeetha Wu, Ren Mieher, Joshua L. Wu, Hui Deivanayagam, Champion |
author_facet | Schormann, Norbert Patel, Manisha Thannickal, Luke Purushotham, Sangeetha Wu, Ren Mieher, Joshua L. Wu, Hui Deivanayagam, Champion |
author_sort | Schormann, Norbert |
collection | PubMed |
description | Streptococcus mutans, found in the human oral cavity, is a significant contributor to the pathogenesis of dental caries. This bacterium expresses three genetically distinct types of glucosyltransferases named GtfB (GTF-I), GtfC (GTF-SI) and GtfD (GTF-S) that play critical roles in the development of dental plaque. The catalytic domains of GtfB, GtfC and GtfD contain conserved active-site residues for the overall enzymatic activity that relate to hydrolytic glycosidic cleavage of sucrose to glucose and fructose, release of fructose and generation of a glycosyl-enzyme intermediate in the reducing end. In a subsequent transglycosylation step, the glucosyl moiety is transferred to the nonreducing end of an acceptor to form a growing glucan polymer chain made up of glucose molecules. It has been proposed that both sucrose breakdown and glucan synthesis occur in the same active site of the catalytic domain, although the active site does not appear to be large enough to accommodate both functions. These three enzymes belong to glycoside hydrolase family 70 (GH70), which shows homology to glycoside hydrolase family 13 (GH13). GtfC synthesizes both soluble and insoluble glucans (α-1,3 and α-1,6 glycosidic linkages), while GtfB and GtfD synthesize only insoluble or soluble glucans, respectively. Here, crystal structures of the catalytic domains of GtfB and GtfD are reported. These structures are compared with previously determined structures of the catalytic domain of GtfC. With this work, apo structures and inhibitor-complex structures with acarbose are now available for the catalytic domains of GtfC and GtfB. The structure of GtfC with maltose allows further identification and comparison of active-site residues. A model of sucrose binding to GtfB is also included. The new structure of the catalytic domain of GtfD affords a structural comparison of the three S. mutans glycosyltransferases. Unfortunately, the catalytic domain of GtfD is not complete since crystallization resulted in the structure of a truncated protein lacking approximately 200 N-terminal residues of domain IV. |
format | Online Article Text |
id | pubmed-10167749 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-101677492023-05-10 The catalytic domains of Streptococcus mutans glucosyltransferases: a structural analysis Schormann, Norbert Patel, Manisha Thannickal, Luke Purushotham, Sangeetha Wu, Ren Mieher, Joshua L. Wu, Hui Deivanayagam, Champion Acta Crystallogr F Struct Biol Commun Research Communications Streptococcus mutans, found in the human oral cavity, is a significant contributor to the pathogenesis of dental caries. This bacterium expresses three genetically distinct types of glucosyltransferases named GtfB (GTF-I), GtfC (GTF-SI) and GtfD (GTF-S) that play critical roles in the development of dental plaque. The catalytic domains of GtfB, GtfC and GtfD contain conserved active-site residues for the overall enzymatic activity that relate to hydrolytic glycosidic cleavage of sucrose to glucose and fructose, release of fructose and generation of a glycosyl-enzyme intermediate in the reducing end. In a subsequent transglycosylation step, the glucosyl moiety is transferred to the nonreducing end of an acceptor to form a growing glucan polymer chain made up of glucose molecules. It has been proposed that both sucrose breakdown and glucan synthesis occur in the same active site of the catalytic domain, although the active site does not appear to be large enough to accommodate both functions. These three enzymes belong to glycoside hydrolase family 70 (GH70), which shows homology to glycoside hydrolase family 13 (GH13). GtfC synthesizes both soluble and insoluble glucans (α-1,3 and α-1,6 glycosidic linkages), while GtfB and GtfD synthesize only insoluble or soluble glucans, respectively. Here, crystal structures of the catalytic domains of GtfB and GtfD are reported. These structures are compared with previously determined structures of the catalytic domain of GtfC. With this work, apo structures and inhibitor-complex structures with acarbose are now available for the catalytic domains of GtfC and GtfB. The structure of GtfC with maltose allows further identification and comparison of active-site residues. A model of sucrose binding to GtfB is also included. The new structure of the catalytic domain of GtfD affords a structural comparison of the three S. mutans glycosyltransferases. Unfortunately, the catalytic domain of GtfD is not complete since crystallization resulted in the structure of a truncated protein lacking approximately 200 N-terminal residues of domain IV. International Union of Crystallography 2023-05-05 /pmc/articles/PMC10167749/ /pubmed/37158310 http://dx.doi.org/10.1107/S2053230X23003199 Text en © Norbert Schormann et al. 2023 https://creativecommons.org/licenses/by/4.0/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. |
spellingShingle | Research Communications Schormann, Norbert Patel, Manisha Thannickal, Luke Purushotham, Sangeetha Wu, Ren Mieher, Joshua L. Wu, Hui Deivanayagam, Champion The catalytic domains of Streptococcus mutans glucosyltransferases: a structural analysis |
title | The catalytic domains of Streptococcus mutans glucosyltransferases: a structural analysis |
title_full | The catalytic domains of Streptococcus mutans glucosyltransferases: a structural analysis |
title_fullStr | The catalytic domains of Streptococcus mutans glucosyltransferases: a structural analysis |
title_full_unstemmed | The catalytic domains of Streptococcus mutans glucosyltransferases: a structural analysis |
title_short | The catalytic domains of Streptococcus mutans glucosyltransferases: a structural analysis |
title_sort | catalytic domains of streptococcus mutans glucosyltransferases: a structural analysis |
topic | Research Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10167749/ https://www.ncbi.nlm.nih.gov/pubmed/37158310 http://dx.doi.org/10.1107/S2053230X23003199 |
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