Structural basis of BMP‐2 and BMP‐7 interactions with antagonists Gremlin‐1 and Noggin in Glioblastoma tumors
| Autor: | Kesaban Sankar Roy Choudhuri, Seema Mishra |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular animal structures Protein Conformation Bone Morphogenetic Protein 7 Cell Bone Morphogenetic Protein 2 010402 general chemistry 01 natural sciences Bone morphogenetic protein 2 0103 physical sciences medicine Humans Histidine Binding site Noggin Binding Sites FoldX 010304 chemical physics Chemistry Tryptophan General Chemistry 0104 chemical sciences Cell biology Bone morphogenetic protein 7 Computational Mathematics medicine.anatomical_structure embryonic structures Intercellular Signaling Peptides and Proteins Thermodynamics Carrier Proteins Glioblastoma Gremlin (protein) Protein Binding |
| Zdroj: | Journal of Computational Chemistry. 41:2544-2561 |
| ISSN: | 1096-987X 0192-8651 |
| DOI: | 10.1002/jcc.26407 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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