Sulfated glycosaminoglycans inhibit transglutaminase 2 by stabilizing its closed conformation

Research output: Contribution to journalResearch articleContributedpeer-review



Transglutaminases (TGs) catalyze the covalent crosslinking of proteins via isopeptide bonds. The most prominent isoform, TG2, is associated with physiological processes such as extracellular matrix (ECM) stabilization and plays a crucial role in the pathogenesis of e.g. fibrotic diseases, cancer and celiac disease. Therefore, TG2 represents a pharmacological target of increasing relevance. The glycosaminoglycans (GAG) heparin (HE) and heparan sulfate (HS) constitute high-affinity interaction partners of TG2 in the ECM. Chemically modified GAG are promising molecules for pharmacological applications as their composition and chemical functionalization may be used to tackle the function of ECM molecular systems, which has been recently described for hyaluronan (HA) and chondroitin sulfate (CS). Herein, we investigate the recognition of GAG derivatives by TG2 using an enzymecrosslinking
activity assay in combination with in silico molecular modeling and docking techniques. The study reveals that GAG represent potent inhibitors of TG2 crosslinking activity and offers atomdetailed mechanistic insights.


Original languageEnglish
Article number13326
Pages (from-to)113326
Number of pages16
JournalScientific Reports
Issue number1
Publication statusPublished - 3 Aug 2022

External IDs

PubMed 35922533
unpaywall 10.1038/s41598-022-17113-2
Scopus 85135313668


Sustainable Development Goals


  • Glycosaminoglycans/metabolism, Heparitin Sulfate/metabolism, Protein Glutamine gamma Glutamyltransferase 2, Transglutaminases/metabolism