Chemical and Physical Biology, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Chemistry. 2011 Sep 26;17(40):11204-9. doi: 10.1002/chem.201101000. Epub 2011 Aug 25.
The interaction of the synthetic pentasaccharide AGAIA(M) (GlcNS,6S-GlcA-GlcNS,3S,6S-IdoA2S-GlcNS,6S-Me) with the extracellular Ig2 domain of the fibroblast growth factor receptor (FGFR2) has been studied by NMR and computational methods. Analysis of the heparin pentasaccharide in the free state and in the complex indicates the existence of a conformational selection process. Although an equilibrium exists between the (1)C(4) and (2)S(0) conformers (ratio 60:40) of the 2-O-sulfo-α-L-iduronate ring (IdoA2S) in the free state, FGFR2 selects only the unique twisted-boat (2)S(0) conformation of this IdoA2S residue. In addition, the protein residues involved in the binding with AGAIA(M) have also been characterized. The NMR results obtained, from both the ligand and protein perspective, were employed to model the bound conformation of the pentasaccharide by a combined docking and molecular dynamic simulation approach.
通过 NMR 和计算方法研究了合成五糖 AGAIA（M）（GlcNS，6S-GlcA-GlcNS，3S，6S-IdoA2S-GlcNS，6S-Me）与成纤维细胞生长因子受体（FGFR2）的细胞外 Ig2 结构域的相互作用。对游离状态和复合物中肝素五糖的分析表明存在构象选择过程。尽管 2-O-磺基-α-L-艾杜糖醛酸环（IdoA2S）在游离状态下（1）C（4）和（2）S（0）构象之间存在平衡，但 FGFR2 仅选择该 IdoA2S 残基的独特扭曲船（2）S（0）构象。此外，还对与 AGAIA（M）结合的蛋白质残基进行了表征。从配体和蛋白质两个角度获得的 NMR 结果，通过结合对接和分子动力学模拟方法来模拟五糖的结合构象。
