Conformation of the pentasaccharide corresponding to the binding site of heparin for antithrombin III |
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Authors: | M Ragazzi D R Ferro B Perly P Sina? M Petitou J Choay |
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Affiliation: | Istituto di Chimica delle Macromolecole del C.N.R., Milano, Italy. |
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Abstract: | The conformation in solution of the pentasaccharide methyl glycoside (As-G-A*-Is-AM; 1), which represents the binding site of heparin for Antithrombin III, has been investigated using molecular mechanics and 1H-n.m.r. spectroscopy. The pentasaccharide has a rather rigid (As-G-A*) and a more flexible (Is-AM) region. A simplified model of 1, comprising two conformations, corresponding to the 1C4 and the 2S0 forms of the iduronate residue, and modified at the G-A* glycosidic linkage with respect to the energy minimum, reproduces most of the observed 3J values and n.O.e. enhancements. The possible role in the binding to Antithrombin III of a low-energy conformer, not observed in solution, is discussed. |
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