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Cited by 13Glycosylation and Glycoproteins ResearchCarbohydrate Chemistry and SynthesisProteoglycans and glycosaminoglycans research

Human neuraminidases have reduced activity towards modified sialic acids on glycoproteins

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Hunter, Carmanah D., Porter, Elizabeth M., Cairo, Christopher W.·2020·Carbohydrate Research
DOI 10.1016/j.carres.2020.108139

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Abstract

Multiple levels of diversity in sialic acid presentation can influence the substrate activity of sialosides for glycoside hydrolases. Few reports have investigated the specificity of human neuraminidase (hNEU) activity towards modified sialic acid residues that can occur on glycoproteins. Previously, we evaluated hNEU activity towards 9-O-acetylated sialic acid in glycolipid substrates and found that hNEU generally discriminated against 9-O-acetylated sialic acid over Neu5Ac. Here, we have investigated the substrate specificity of hNEU enzymes for a glycoprotein substrate (bovine submaxillary mucin) containing 9-O-acetylated and Neu5Gc residues. Using this model substrate, we observe a general trend for hNEU tolerance of Neu5Ac > Neu5Gc ≫ Neu5,9Ac 2, consistent with our previous results with glycolipid substrates. These results expand our understanding of hNEU enzyme specificity and suggest that naturally occurring modifications of sialic acids can play a role in regulating hNEU activity.

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  • The widely open active site explains why O9-acetylation reduces activity by up to 90% in NEU2, NEU3, and NEU4 but only 50% in NEU1.

    “This widely open active site explains why substrate O9-acetylation reduces activity by up to 90% in NEU2, NEU3, and NEU4 but only 50% in NEU1 (72, 73).”

    From Structure of the immunoregulatory sialidase NEU1 (2023) · cites this paper as [73]

    The Results and Discussion report a roughly 9- to 16-fold preference for unmodified sialic acid in NEU2–NEU4 and at least a 1.5- to 2-fold preference in NEU1, broadly supporting reduced activity toward O9-acetylated substrate. They do not establish that NEU1 activity falls by only 50%: its estimate is a lower bound, and the authors say more sensitive methods are needed to determine whether NEU1 differs from the other enzymes. The paper attributes NEU2’s strict tolerance to a constrained C9 active-site pocket, not a widely open active site. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • NEU1 is the least affected by presence of an N5-glycolyl group.

    “NEU1 is also the least affected by presence of an N5-glycolyl group, which is slightly larger than N5-acetyl (73).”

    From Structure of the immunoregulatory sialidase NEU1 (2023) · cites this paper as [73]

    The Results and Discussion (page unavailable) report that all human neuraminidase isoenzymes moderately prefer Neu5Ac over Neu5Gc, the N5-glycolyl form, and that this preference is most pronounced in NEU3. The text does not establish that NEU1 is the least affected of the isoenzymes. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Hunter, C. D., Porter, E. M., & Cairo, C. W.
Affiliations
University of Alberta (CA)
Corresponding author
Cairo, Christopher W.
ORCID
Venue
Carbohydrate Research
Publisher
Elsevier BV
Published
2020-11
Volume
497
Pages
108139
ISSN
0008-6215 (ISSN-L)
DOI
10.1016/j.carres.2020.108139
OpenAlex
W3082427123
Cited by
13
References
1
Citations by year
2026: 3 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4
FWCI
0.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Carbohydrate Research (publishedVersion)
  • ChemRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Royal College of Surgeons in Ireland (submittedVersion)
Funders
  • Natural Sciences and Engineering Research Council of Canada
  • Alberta Glycomics Centre
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Keywords
sialic acid modification, N-glycolylneuraminic acid, glycoproteins, substrate specificity, bovine submaxillary mucin, glycolipids, sialosides
MeSH terms
Acetylation, Animals, Cattle, Humans, Mucins, Neuraminidase, Sialic Acids, Substrate Specificity

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