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Structural basis of BMP‐2 and BMP‐7 interactions with antagonists Gremlin‐1 and Noggin in Glioblastoma tumors
Author(s) -
Choudhuri Kesaban Sankar Roy,
Mishra Seema
Publication year - 2020
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.26407
Subject(s) - noggin , bone morphogenetic protein , chemistry , bone morphogenetic protein 2 , microbiology and biotechnology , bone morphogenetic protein 7 , bmpr2 , glioblastoma , cancer research , biology , biochemistry , gene , in vitro
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.