A 3D-structural model of unsulfated chondroitin from high-field NMR: 4-sulfation has little effect on backbone conformation.
A 3D-structural model of unsulfated chondroitin from high-field NMR: 4-sulfation has little effect on backbone conformation.
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DOI：
10.1016/j.carres.2009.11.013
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发表时间：
2010-01-26
影响因子：
3.1
通讯作者：
Almond, Andrew
中科院分区：
文献类型：
--
作者：
Sattelle, Benedict M.;Shakeri, Javad;Roberts, Ian S.;Almond, Andrew
硫酸糖胺聚糖软骨素在人类健康和疾病中是必不可少的，但硫酸化如何在原子水平上决定其3D结构尚不清楚。为了解决这个问题，我们纯化了未硫酸化软骨素的均质寡糖（有和没有15 N富集），并通过高场NMR对其进行分析，以比较已发表的硫酸软骨素和透明质酸的3D结构。结果是第一个完整的四糖分配和六糖的实验3D模型（PDB代码2KQO）。与透明质酸一样，我们确认酰胺质子不参与强的、持久的残基间氢键。然而，与透明质酸相反，在己糖胺OH-4和葡萄糖醛酸O 5原子之间未推断出氢键穿过β（1→3）糖苷键。未硫酸化的软骨素键几何形状与透明质酸略有不同，围绕β（1→3）ψ二面角旋转（如之前通过模拟预测的那样），而β（1→4）键不受影响。此外，比较表明，这种糖苷键的几何形状是类似的软骨素-4-硫酸。因此，我们假设，两个氨基己糖OH-4和OH-6原子的溶剂暴露在软骨素，解释了为什么它是经得起硫酸化和透明质酸是不是，以及4-硫酸化对骨架构象几乎没有影响。我们的结论证实了本文提出的三维模型的价值，并促进了我们对糖胺聚糖分子性质的理解。
The glycosaminoglycan chondroitin sulfate is essential in human health and disease but exactly how sulfation dictates its 3D-strucutre at the atomic level is unclear. To address this, we have purified homogenous oligosaccharides of unsulfated chondroitin (with and without 15N-enrichment) and analysed them by high-field NMR to make a comparison published chondroitin sulfate and hyaluronan 3D-structures. The result is the first full assignment of the tetrasaccharide and an experimental 3D-model of the hexasaccharide (PDB code 2KQO). In common with hyaluronan, we confirm that the amide proton is not involved in strong, persistent inter-residue hydrogen bonds. However, in contrast to hyaluronan, a hydrogen bond is not inferred between the hexosamine OH-4 and the glucuronic acid O5 atoms across the β(1→3) glycosidic linkage. The unsulfated chondroitin bond geometry differs slightly from hyaluronan by rotation about the β(1→3) ψ dihedral (as previously predicted by simulation), while the β(1→4) linkage is unaffected. Furthermore, comparison shows that this glycosidic linkage geometry is similar in chondroitin-4-sulfate. We therefore hypothesise that both hexosamine OH-4 and OH-6 atoms are solvent exposed in chondroitin, explaining why it is amenable to sulfation and hyaluronan is not, and also that 4-sulfation has little effect on backbone conformation. Our conclusions exemplify the value of the 3D-model presented here and progress our understanding of glycosaminoglycan molecular properties.
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影响因子：
5.6
作者：
Huang, WJ;Matte, A;Cygler, M
通讯作者：
Cygler, M
影响因子：
5.6
作者：
Almond, A;DeAngelis, PL;Blundell, CD
通讯作者：
Blundell, CD
DOI：
10.1046/j.1432-1327.2001.01948.x
发表时间：
2001-03-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Huckerby, TN;Lauder, RM;Weeks, SD
通讯作者：
Weeks, SD
影响因子：
5.6
作者：
DYSON, HJ;RANCE, M;WRIGHT, PE
通讯作者：
WRIGHT, PE
影响因子：
4.1
作者：
Blundell, Charles D.;DeAngelis, Paul L.;Almond, Andrew
通讯作者：
Almond, Andrew