Evidence map›Paper›PMID 30788513›Full record

ArticleCellular and molecular life sciences : CMLS2019

Expression and purification of recombinant extracellular sulfatase HSulf-2 allows deciphering of enzyme sub-domain coordinated role for the binding and 6-O-desulfation of heparan sulfate.

Amal Seffouh, Rana El Masri, Olga Makshakova, Evelyne Gout, Zahra El Oula Hassoun, Jean-Pierre Andrieu, Hugues Lortat-Jacob, Romain R Vivès

Open access · greenAbstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-weighted citation impact, top 22% 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

13 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Article
  3. The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue-Specific Perspectives.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  4. Article
  5. Myeloid deficiency of heparan sulfate 6-O-endosulfatases impairs bone marrow hematopoiesis.Matrix biology : journal of the International Society for Matrix Biology · 2024
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Loss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses.American journal of physiology. Lung cellular and molecular physiology · 2019
    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

8 authors at 5 institutions in 2 countries.

Amal SeffouhUniv. Grenoble Alpes, CNRS, CEA, IBS, 38000 Grenoble, France.
Rana El MasriUniv. Grenoble Alpes, CNRS, CEA, IBS, 38000 Grenoble, France.
Olga MakshakovaKazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Kazan, Russian Federation.
Evelyne GoutUniv. Grenoble Alpes, CNRS, CEA, IBS, 38000 Grenoble, France.
Zahra El Oula HassounUniv. Grenoble Alpes, CNRS, CEA, IBS, 38000 Grenoble, France.
Jean-Pierre AndrieuUniv. Grenoble Alpes, CNRS, CEA, IBS, 38000 Grenoble, France.
Hugues Lortat-JacobUniv. Grenoble Alpes, CNRS, CEA, IBS, 38000 Grenoble, France.
Romain R VivèsUniv. Grenoble Alpes, CNRS, CEA, IBS, 38000 Grenoble, France. romain.vives@ibs.fr.
Commissariat à l'Énergie Atomique et aux Énergies Alternatives · FRCentre National de la Recherche Scientifique · FRInstitut de Biologie Structurale · FRKazan Institute of Biochemistry and Biophysics · RUUniversité Grenoble Alpes · FR

Funding

Agence Nationale de la Recherche ANR-10-INSB-05-02Agence Nationale de la Recherche ANR-10-LABX-49-01Agence Nationale de la Recherche ANR-12-BSV8-0023Agence Nationale de la Recherche ANR-15-IDEX-02Agence Nationale de la Recherche ANR-17-CE11-0040Communaut? Universit? Grenoble?Alpes UGA AGIR program 2016
6 · The paper itself

Abstract

Through their ability to edit 6-O-sulfation pattern of Heparan sulfate (HS) polysaccharides, Sulf extracellular endosulfatases have emerged as critical regulators of many biological processes, including tumor progression. However, study of Sulfs remains extremely intricate and progress in characterizing their functional and structural features has been hampered by limited access to recombinant enzyme. In this study, we unlock this critical bottleneck, by reporting an efficient expression and purification system of recombinant HSulf-2 in mammalian HEK293 cells. This novel source of enzyme enabled us to investigate the way the enzyme domain organization dictates its functional properties. By generating mutants, we confirmed previous studies that HSulf-2 catalytic (CAT) domain was sufficient to elicit arylsulfatase activity and that its hydrophilic (HD) domain was necessary for the enzyme 6-O-endosulfatase activity. However, we demonstrated for the first time that high-affinity binding of HS substrates occurred through the coordinated action of both domains, and we identified and characterized 2 novel HS binding sites within the CAT domain. Altogether, our findings contribute to better understand the molecular mechanism governing HSulf-2 substrate recognition and processing. Furthermore, access to purified recombinant protein opens new perspectives for the resolution of HSulf structure and molecular features, as well as for the development of Sulf-specific inhibitors.

Indexed as

Binding SitesCatalytic DomainCell LineHEK293 CellsHeparan SulfateHumansHydrophobic and Hydrophilic InteractionsModels, MolecularProtein BindingRecombinant ProteinsStructure-Activity RelationshipSubstrate SpecificitySulfatasesSulfotransferasesHeparan SulfateRecombinant ProteinsSULF2 protein, humanSulfatasesSulfotransferasesExtracellular matrixGlycocalyxGlycosaminoglycanHeparinStructure–function relationships

Identifiers

PMID30788513
PMCPMC11105607
OpenAlexW2917503581

What OpenQuestion holds

Textmetadata
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.