Conformational dynamics of sialyl Lewisx in aqueous solution and its interaction with selectinE.: A study by molecular dynamics

被引:25
作者
Veluraja, K
Margulis, CJ [1 ]
机构
[1] Univ Iowa, Dept Chem 319 CB, Iowa City, IA 52242 USA
[2] Manonmaniam Sundaranar Univ, Dept Phys, Tirunelveli, Tamil Nadu, India
关键词
D O I
10.1080/07391102.2005.10507051
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Three dimensional structures of sialyl Lewis(x) (SLe(x)) in aqueous solution and bound to selectinE are described based on an exhaustive conformational analysis and several long molecular dynamics simulations using different glycosidic regions as starting conformations. It appears from this study that when the oligosaccharide is free in solution the NeuNAc alpha(2-3)Gal segment favors glycosidic conformation in three different regions in the (Phi,psi) plane with propensity of populations in the ratio 1: 8: 1. Each one of these structures is characteristically stabilized by specific hydrogen bonding interaction between NeuNAc and Gal. On the other hand, the Gal-GlcNAc-Fuc segment can exist in four different conformational states. Based on the topology of SLex we are able to predict that out of all the allowed conformations in solution only two of these structures possess a geometry that would fit without steric clashes into the binding location of selectinE. In both of these binding modes, segment Gal-GIcNAc-Fuc adopts a unique conformation. The only difference between the two SLex conformers that can successfully bind to selectinE is given by two possible regions in glycosidic space in the fragment NeuNAca(2-3)Gal. A large conformational departure from the crystallographic data is observed for two lysine residues at the binding site of selectin E. These two residues play an important role when SLex binds selectinE in aqueous solution. These findings help reconcile the X-ray data, in which these residues appear to be 1 nm away from SLex, with recent liquid NMR data reporting couplings between these protein residues and the sugar.
引用
收藏
页码:101 / 111
页数:11
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