Generating orthogonal glycosyltransferase and nucleotide sugar pairs as next-generation glycobiology tools
File(s)
Published version
Author(s)
Cioce, Anna
Malaker, Stacy A
Schumann, Benjamin
Type
Journal Article
Abstract
Protein glycosylation fundamentally impacts biological processes. Nontemplated biosynthesis introduces unparalleled complexity into glycans that needs tools to understand their roles in physiology. The era of quantitative biology is a great opportunity to unravel these roles, especially by mass spectrometry glycoproteomics. However, with high sensitivity come stringent requirements on tool specificity. Bioorthogonal metabolic labeling reagents have been fundamental to studying the cell surface glycoproteome but typically enter a range of different glycans and are thus of limited specificity. Here, we discuss the generation of metabolic 'precision tools' to study particular subtypes of the glycome. A chemical biology tactic termed bump-and-hole engineering generates mutant glycosyltransferases that specifically accommodate bioorthogonal monosaccharides as an enabling technique of glycobiology. We review the groundbreaking discoveries that have led to applying the tactic in the living cell and the implications in the context of current developments in mass spectrometry glycoproteomics.
Date Issued
2021-02-01
Date Acceptance
2020-09-01
Citation
Current Opinion in Chemical Biology, 2021, 60, pp.66-78
ISSN
1367-5931
Publisher
Elsevier
Start Page
66
End Page
78
Journal / Book Title
Current Opinion in Chemical Biology
Volume
60
Copyright Statement
© 2020 The Author(s). Published by Elsevier Ltd. This is an
open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
(http://creativecommons.org/licenses/by/4.0/
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33125942
PII: S1367-5931(20)30122-8
Subjects
Bioorthogonal
Click chemistry
Glycoprotein
Glycosylation
Glycosyltransferase
Mucin
Protein engineering
Animals
Glycomics
Glycosyltransferases
Humans
Nucleotides
Sugars
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2020-10-27