A mechanism for bistability in glycosylation
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Journal ArticleDate:
2018Access:
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Mc Donald, A., Tipton, K., Davey, G. A mechanism for bistability in glycosylation, PLOS Computational Biology, 2018, 14, 8, e1006348Download Item:
Abstract:
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.
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Grant Number
Science Foundation Ireland
SFI-13/SPSSPC/I2893
Author's Homepage:
http://people.tcd.ie/gdaveyhttp://people.tcd.ie/amcdonld
http://people.tcd.ie/ktipton
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PLOS Computational Biology;14;
8;
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Full text availableKeywords:
Glycosyltransferases, Enzymes, Kinetic mechanism, Glycan products, Cancer cells, Glycosyl epitopesSubject (TCD):
Cancer , Immunology, Inflammation & Infection , Neuroscience , BISTABILITY , Computational Biology , ENZYME KINETICSDOI:
https://doi.org/10.1371/journal.pcbi.1006348Metadata
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