Sulfated glycosaminoglycans inhibit transglutaminase 2 by stabilizing its closed conformation

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

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.

Details

OriginalspracheEnglisch
Aufsatznummer13326
Seiten (von - bis)113326
Seitenumfang16
FachzeitschriftScientific Reports
Jahrgang12
Ausgabenummer1
PublikationsstatusVeröffentlicht - 3 Aug. 2022
Peer-Review-StatusJa

Externe IDs

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

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

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