Abstract
The binding site and backbone dynamics of a bioactive complex formed by the acidic fibroblast growth factor (FGF-1) and a specifically designed heparin hexasaccharide has been investigated by HSQC and relaxation NMR methods. The comparison of the relaxation data for the free and bound states has allowed showing that the complex is monomeric, and still induces mutagenesis, and that the protein backbone presents reduced motion in different timescale in its bound state, except in certain points that are involved in the interaction with the fibroblast growth factor receptor (FGFR).
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Acknowledgements
We thank Mrs. Mercedes Zazo for her help during the expression and purification of labelled FGF-1. This work was supported by the Dirección General de Investigación Científica y Técnica (Grants BQU2000-1501-C02-01, BQU2002-0374, and BQU2003-03550-C03-01). We are indebted to Dr Dosset and Dr Guenneugues for kindly providing the programmes TENSOR2 and anal_roe, respectively. We also thank Comunidad de Madrid, Fundación Ramón Areces, and Fundación Francisco Cobos for fellowships to R.F., J.A., and R.O., respectively. NMR time from the Parc Cientific of Barcelona (Dr. M. Gairí), University of Santiago de Compostela, and CAI-NMR of Universidad Complutense is warmly thanked.
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Angeles Canales-Mayordomo and Rosa Fayos have contributed equally to this research.
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Canales-Mayordomo, A., Fayos, R., Angulo, J. et al. Backbone dynamics of a biologically active human FGF-1 monomer, complexed to a hexasaccharide heparin-analogue, by 15N NMR relaxation methods. J Biomol NMR 35, 225–239 (2006). https://doi.org/10.1007/s10858-006-9024-y
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DOI: https://doi.org/10.1007/s10858-006-9024-y