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A mechanism for bistability in glycosylation
Glycosyltransferases are a class of enzymes that catalyse the posttranslational modification of proteins to produce a large number of glycoconjugate acceptors from a limited number of nucleotide-sugar donors. The products of one glycosyltransferase can be the substrates of several other enzymes, cau...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093706/ https://www.ncbi.nlm.nih.gov/pubmed/30074989 http://dx.doi.org/10.1371/journal.pcbi.1006348 |
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author | McDonald, Andrew G. Tipton, Keith F. Davey, Gavin P. |
author_facet | McDonald, Andrew G. Tipton, Keith F. Davey, Gavin P. |
author_sort | McDonald, Andrew G. |
collection | PubMed |
description | Glycosyltransferases are a class of enzymes that catalyse the posttranslational modification of proteins to produce a large number of glycoconjugate acceptors from a limited number of nucleotide-sugar donors. The products of one glycosyltransferase can be the substrates of several other enzymes, causing a combinatorial explosion in the number of possible glycan products. The kinetic behaviour of systems where multiple acceptor substrates compete for a single enzyme is presented, and the case in which high concentrations of an acceptor substrate are inhibitory as a result of abortive complex formation, is shown to result in non-Michaelian kinetics that can lead to bistability in an open system. A kinetic mechanism is proposed that is consistent with the available experimental evidence and provides a possible explanation for conflicting observations on the β-1,4-galactosyltransferases. Abrupt switching between steady states in networks of glycosyltransferase-catalysed reactions may account for the observed changes in glycosyl-epitopes in cancer cells. |
format | Online Article Text |
id | pubmed-6093706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-60937062018-08-30 A mechanism for bistability in glycosylation McDonald, Andrew G. Tipton, Keith F. Davey, Gavin P. PLoS Comput Biol Research Article Glycosyltransferases are a class of enzymes that catalyse the posttranslational modification of proteins to produce a large number of glycoconjugate acceptors from a limited number of nucleotide-sugar donors. The products of one glycosyltransferase can be the substrates of several other enzymes, causing a combinatorial explosion in the number of possible glycan products. The kinetic behaviour of systems where multiple acceptor substrates compete for a single enzyme is presented, and the case in which high concentrations of an acceptor substrate are inhibitory as a result of abortive complex formation, is shown to result in non-Michaelian kinetics that can lead to bistability in an open system. A kinetic mechanism is proposed that is consistent with the available experimental evidence and provides a possible explanation for conflicting observations on the β-1,4-galactosyltransferases. Abrupt switching between steady states in networks of glycosyltransferase-catalysed reactions may account for the observed changes in glycosyl-epitopes in cancer cells. Public Library of Science 2018-08-03 /pmc/articles/PMC6093706/ /pubmed/30074989 http://dx.doi.org/10.1371/journal.pcbi.1006348 Text en © 2018 McDonald et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article McDonald, Andrew G. Tipton, Keith F. Davey, Gavin P. A mechanism for bistability in glycosylation |
title | A mechanism for bistability in glycosylation |
title_full | A mechanism for bistability in glycosylation |
title_fullStr | A mechanism for bistability in glycosylation |
title_full_unstemmed | A mechanism for bistability in glycosylation |
title_short | A mechanism for bistability in glycosylation |
title_sort | mechanism for bistability in glycosylation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093706/ https://www.ncbi.nlm.nih.gov/pubmed/30074989 http://dx.doi.org/10.1371/journal.pcbi.1006348 |
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