Evidence map›Paper›PMID 35405095›Full record

ArticleThe Journal of biological chemistry2022

Structure-guided mutagenesis of a mucin-selective metalloprotease from Akkermansia muciniphila alters substrate preferences.

D Judy Shon, Daniel Fernandez, Nicholas M Riley, Michael J Ferracane, Carolyn R Bertozzi

Open access · goldAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 28 citations in OpenAlex.

  1. Discovery of a secretedGut microbes · 2026
    Article
  2. Article
  3. Deep Learning Prediction of O-Glycopeptide Tandem Mass Spectra Enhances O-Glycoproteomics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Total flavonoids fromAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2026
    Article
  5. The VaginalMicroorganisms · 2026
    Article
  6. Article
  7. Article
  8. The Biology ofAnnual review of microbiology · 2025
    Review
  9. Review
  10. Review
  11. mBio · 2024
    Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. DecipheringMolecular omics · 2022
    Article
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

D Judy ShonDepartment of Chemistry and Stanford ChEM-H, Stanford University, Stanford, California, USA.
Daniel FernandezStanford ChEM-H Macromolecular Structure Knowledge Center, Stanford University, Stanford, California, USA.
Nicholas M RileyDepartment of Chemistry and Stanford ChEM-H, Stanford University, Stanford, California, USA.
Michael J FerracaneDepartment of Chemistry, University of Redlands, Redlands, California, USA.
Carolyn R BertozziDepartment of Chemistry and Stanford ChEM-H, Stanford University, Stanford, California, USA; Howard Hughes Medical Institute, Stanford University, Stanford, California, USA. Electronic address: bertozzi@stanford.edu.
Stanford University · USHoward Hughes Medical Institute · USUniversity of Redlands · US

Funding

X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Investigating the Surface GlycoproteomeR01CA200423 · NCI · STANFORD UNIVERSITY · PI Carolyn Bertozzi · 2015 to 2026
$3.8M
Uniting Mass Spectrometry and Glycoscience to Investigate Cancer BiologyK00CA212454 · NCI · STANFORD UNIVERSITY · PI RILEY, NICHOLAS M · 2018 to 2021
$331k
NCI NIH HHS K00 CA212454NCI NIH HHS R01 CA200423NIGMS NIH HHS P41 GM103393
6 · The paper itself

Abstract

Akkermansia muciniphila, a mucin-degrading microbe found in the human gut, is often associated with positive health outcomes. The abundance of A. muciniphila is modulated by the presence and accessibility of nutrients, which can be derived from diet or host glycoproteins. In particular, the ability to degrade host mucins, a class of proteins carrying densely O-glycosylated domains, provides a competitive advantage in the sustained colonization of niche mucosal environments. Although A. muciniphila is known to rely on mucins as a carbon and nitrogen source, the enzymatic machinery used by this microbe to process mucins in the gut is not yet fully characterized. Here, we focus on the mucin-selective metalloprotease, Amuc_0627 (AM0627), which is known to cleave between adjacent residues carrying truncated core 1 O-glycans. We showed that this enzyme is capable of degrading purified mucin 2 (MUC2), the major protein component of mucus in the gut. An X-ray crystal structure of AM0627 (1.9 Å resolution) revealed O-glycan-binding residues that are conserved between structurally characterized enzymes from the same family. We further rationalized the substrate cleavage motif using molecular modeling to identify nonconserved glycan-interacting residues. We conclude that mutagenesis of these residues resulted in altered substrate preferences down to the glycan level, providing insight into the structural determinants of O-glycan recognition.

Indexed as

MucinsAkkermansiaHumansMetalloproteasesMutagenesisVerrucomicrobiaMetalloproteasesMucinsenzyme structureglycoproteomicsmetalloproteasemicrobiomemolecular dockingmucinmucinaseO-glycosylationX-ray crystallography

Identifiers

PMID35405095
PMCPMC9118916
OpenAlexW4223459555

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.