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Open AccessArticle

Analysis of Procollagen C-Proteinase Enhancer-1/Glycosaminoglycan Binding Sites and of the Potential Role of Calcium Ions in the Interaction

1
Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland
2
Institute of Chemistry and Biochemistry, Free University of Berlin, Takustr. 3, 14195 Berlin, Germany
3
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, 1117 Budapest, Hungary
4
MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, Budapest 112, P.O. Box 32, 1518 Budapest, Hungary
5
Maurice and Gabriela Goldschleger Eye Research Institute, Tel-Aviv University Sackler Faculty of Medicine, Sheba Medical Center, Tel-Hashomer, 52621 Ramat Gan, Israel
6
Institute of Molecular and Supramolecular Chemistry and Biochemistry, UMR 5246, CNRS, INSA Lyon, CPE, University Claude Bernard Lyon 1, Univ Lyon, 69622 Villeurbanne CEDEX, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(20), 5021; https://doi.org/10.3390/ijms20205021
Received: 13 September 2019 / Revised: 7 October 2019 / Accepted: 9 October 2019 / Published: 10 October 2019
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. View Full-Text
Keywords: procollagen C-proteinase enhancer-1; glycosaminoglycans; computational analysis of protein-glycosaminoglycan interactions; calcium ions; fragment-based docking procollagen C-proteinase enhancer-1; glycosaminoglycans; computational analysis of protein-glycosaminoglycan interactions; calcium ions; fragment-based docking
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MDPI and ACS Style

Potthoff, J.; Bojarski, K.K.; Kohut, G.; Lipska, A.G.; Liwo, A.; Kessler, E.; Ricard-Blum, S.; Samsonov, S.A. Analysis of Procollagen C-Proteinase Enhancer-1/Glycosaminoglycan Binding Sites and of the Potential Role of Calcium Ions in the Interaction. Int. J. Mol. Sci. 2019, 20, 5021.

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