Analysis of Procollagen C-Proteinase Enhancer-1/Glycosaminoglycan Binding Sites and of the Potential Role of Calcium Ions in the Interaction
| Autor: | Sergey A. Samsonov, Jan Potthoff, Sylvie Ricard-Blum, Gergely Kohut, Krzysztof K. Bojarski, Efrat Kessler, Agnieszka G. Lipska, Adam Liwo |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Models Molecular procollagen c-proteinase enhancer-1 Molecular model Protein Conformation In silico Context (language use) Catalysis Article fragment-based docking Inorganic Chemistry Glycosaminoglycan lcsh:Chemistry 03 medical and health sciences Sulfation Protein Interaction Domains and Motifs Amino Acid Sequence Physical and Theoretical Chemistry Surface plasmon resonance Molecular Biology lcsh:QH301-705.5 Spectroscopy Ions calcium ions Glycosaminoglycan binding Extracellular Matrix Proteins Binding Sites 030102 biochemistry & molecular biology Chemistry Organic Chemistry General Medicine computational analysis of protein-glycosaminoglycan interactions Computer Science Applications Molecular Docking Simulation Procollagen peptidase 030104 developmental biology glycosaminoglycans lcsh:Biology (General) lcsh:QD1-999 Biophysics Calcium |
| Zdroj: | International Journal of Molecular Sciences, Vol 20, Iss 20, p 5021 (2019) International Journal of Molecular Sciences Volume 20 Issue 20 |
| Popis: | In this study, we characterize the interactions between the extracellular matrix protein, procollagen C-proteinase enhancer-1 (PCPE-1), and glycosaminoglycans (GAGs), which are linear anionic periodic polysaccharides. We applied molecular modeling approaches to build a structural model of full-length PCPE-1, which is not experimentally available, to predict GAG binding poses for various GAG lengths, types and sulfation patterns, and to determine the effect of calcium ions on the binding. The computational data are analyzed and discussed in the context of the experimental results previously obtained using surface plasmon resonance binding assays. We also provide experimental data on PCPE-1/GAG interactions obtained using inhibition assays with GAG oligosaccharides ranging from disaccharides to octadecasaccharides. Our results predict the localization of GAG-binding sites at the amino acid residue level onto PCPE-1 and is the first attempt to describe the effects of ions on protein-GAG binding using modeling approaches. In addition, this study allows us to get deeper insights into the in silico methodology challenges and limitations when applied to GAG-protein interactions. |
| Databáze: | OpenAIRE |
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