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...

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Bibliographic Details
Published in:PLoS computational biology 2018-08, Vol.14 (8), p.e1006348-e1006348
Main Authors: McDonald, Andrew G, Tipton, Keith F, Davey, Gavin P
Format: Article
Language:English
Subjects:
Biochemistry
Biology and Life Sciences
Bistability
Catalysis
Combinatorial analysis
Complex formation
Enzymes
Epitopes
Equilibrium
Glycan
Glycoproteins
Glycosylation
Glycosyltransferase
Glycosyltransferases
Immunology
Kinases
Kinetics
Metabolism
Nucleotides
Open systems
Physiological aspects
Protein research
Reaction kinetics
Software
Substrate inhibition
Substrates
Sugar
Switching theory
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Summary: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.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1006348