期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 26, 期 67, 页码 15643-15653出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202003212
关键词
allostery; blood group antigens; galectin; glycan molecular recognition; NMR spectroscopy
资金
- European Research Council (ERC) [788143-RECGLYCANMR]
- Agencia Estatal Investigacion of Spain (AEI) [RTI2018-094751-B-C21, RTI2018-099592-B-C22, RTI2018-101269-B-I00]
- Ramon y Cajal Contract
- Severo Ochoa Excellence Accreditation [SEV-2016-0644]
- Instituto de Salud Carlos III of Spain, ISCIII [PRB3 IPT17/0019]
- Mizutani Foundation for Glycoscience [200077]
The interaction of human galectin-1 with a variety of oligosaccharides, from di-(N-acetyllactosamine) to tetra-saccharides (blood B type-II antigen) has been scrutinized by using a combined approach of different NMR experiments, molecular dynamics (MD) simulations, and isothermal titration calorimetry. Ligand- and receptor-based NMR experiments assisted by computational methods allowed proposing three-dimensional structures for the different complexes, which explained the lack of enthalpy gain when increasing the chemical complexity of the glycan. Interestingly, and independently of the glycan ligand, the entropy term does not oppose the binding event, a rather unusual feature for protein-sugar interactions. CLEANEX-PM and relaxation dispersion experiments revealed that sugar binding affected residues far from the binding site and described significant changes in the dynamics of the protein. In particular, motions in the microsecond-millisecond timescale in residues at the protein dimer interface were identified in the presence of high affinity ligands. The dynamic process was further explored by extensive MD simulations, which provided additional support for the existence of allostery in glycan recognition by human galectin-1.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据