Structural basis of BMP-2 and BMP-7 interactions with antagonists Gremlin-1 and Noggin in Glioblastoma tumors.

TitleStructural basis of BMP-2 and BMP-7 interactions with antagonists Gremlin-1 and Noggin in Glioblastoma tumors.
Publication TypeJournal Article
Year of Publication2020
AuthorsChoudhuri KSankar Roy, Mishra S
JournalJ Comput Chem
Date Published2020 Sep 15
ISSN1096-987X
Abstract

In Glioblastoma (GBM) brain tumors, both Gremlin-1 and Noggin are reported to bind to BMP and inhibit BMP-signaling, thereby allowing the cell to maintain tumorous morphology. Enlisting the interfacial residues important for protein-protein complex formation between BMPs (BMP-2 and BMP-7) and antagonists (Gremlin-1 and Noggin), we analyzed the structural basis of their interactions. We found possible key mutations that destabilize these complexes, which may prevent GBM development. It was also observed that when the interfacial residues were either mutated to histidine or tryptophan, it led to higher destabilization energy values. Besides, our study of the Noggin interactive model of BMP-2 suggested preferential binding at binding site II over binding site I. In the case of Gremlin-1 and BMPs, our research, along with few previous studies, indicates a close-ended cis-trans interactive model.

DOI10.1002/jcc.26407
Alternate JournalJ Comput Chem
PubMed ID32935366