5 NANOSECOND MOLECULAR-DYNAMICS AND NMR-STUDY OF CONFORMATIONAL TRANSITIONS IN THE SIALYL-LEWIS-X ANTIGEN

被引:76
作者
RUTHERFORD, TJ [1 ]
SPACKMAN, DG [1 ]
SIMPSON, PJ [1 ]
HOMANS, SW [1 ]
机构
[1] UNIV READING,DEXTRA LABS LTD,READING RG6 2BX,ENGLAND
基金
英国惠康基金;
关键词
CONFORMATIONAL TRANSITIONS; MOLECULAR DYNAMICS; NMR; SIALYL-LEWIS X; OLIGOSACCHARIDE CONFORMATION;
D O I
10.1093/glycob/4.1.59
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
The range of internal motions of the sialyl Lewis-X (SLe(x)) tetrasaccharide (NeuNAc alpha 2-->3Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc) [where Fuc is L-fucopyranose, Gal is D-galactopyranose, GlcNAc is 2-acetamido-2-deoxy-D-glucopyranose and NeuNAc is D-neuraminic acid (sialic acid)] was studied by restrained simulated annealing and restrained molecular dynamics (MD) calculations. Transitions between predominantly two conformational states were observed for the NeuNAc alpha (2-->3)Gal linkage, consistent with previous observations for this linkage in sialyl-N-acetyllactosamine. The Mn trajectory was simulated for 5 ns of real time, in order to observe a statistically significant number of these relatively low-frequency transitions. The Fuc alpha(1-->3)GlcNAc and Gal beta (1-->4)GlcNAc linkages, however, showed more restricted flexibility within a single energy well (RMS differences for the time-averaged glycosidic torsion angles, <phi> and <psi>, were 50% lower than for the NeuNAc alpha(2-->3)Gal linkage), and approximate to a rigid conformation. MMR parameters [relative rotating-frame Overhauser enhancement (r.O.e.) and inter-glycosidic (3)J(CH)] back-calculated from the Mn simulation were in close agreement with experimentally measured values for the free reducing oligosaccharide in D2O solution.
引用
收藏
页码:59 / 68
页数:10
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