Structural Basis for Aza-Glycine Stabilization of Collagen
Structural Basis for Aza-Glycine Stabilization of Collagen
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DOI：
10.1021/jacs.7b03398
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发表时间：
2017-07-19
影响因子：
15
通讯作者：
Chenoweth, David M.
中科院分区：
文献类型：
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作者：
Kasznel, Alexander J.;Zhang, Yitao;Chenoweth, David M.
以前，我们已经证明用氮杂-甘氨酸取代胶原蛋白中严格保守的甘氨酸提供了稳定三螺旋胶原蛋白肽的一般解决方案（Chenoweth，D. M.;等，J. Am. 2016，138，9751; 2015，137，12422）。氮杂-甘氨酸提供的额外氢键和构象约束增加了由Pro-Hyp-Gly三联体重复组成的胶原肽的热稳定性和折叠速率，允许截短为迄今为止观察到的最小自组装肽系统。在这里，我们表明，氮杂-甘氨酸取代增强了稳定的含精氨酸的胶原蛋白肽，并提供了一个原子分辨率的晶体结构的稳定的结构基础。这些结果表明，单个氮原子取代甘氨酸α碳使肽的三螺旋解链温度增加8.6 ℃。此外，我们提供了第一个稳定的三螺旋胶原蛋白肽含有氮杂-甘氨酸的结构基础，我们表明，最小的改变发生的肽骨架构象与氮杂-甘氨酸掺入。
Previously, we have demonstrated that replacement of the strictly conserved glycine in collagen with aza-glycine provides a general solution for stabilizing triple helical collagen peptides (Chenoweth, D. M.; et al. J. Am. Chem. Soc. 2016, 138, 9751; 2015, 137, 12422). The additional hydrogen bond and conformational constraints provided by aza-glycine increases the thermal stability and rate of folding in collagen peptides composed of Pro-Hyp-Gly triplet repeats, allowing for truncation to the smallest self-assembling peptide systems observed to date. Here we show that aza-glycine substitution enhances the stability of an arginine-containing collagen peptide and provide a structural basis for this stabilization with an atomic resolution crystal structure. These results demonstrate that a single nitrogen atom substitution for a glycine alpha carbon increases the peptide's triple helix melting temperature by 8.6 degrees C. Furthermore, we provide the first structural basis for stabilization of triple helical collagen peptides containing aza-glycine and we demonstrate that minimal alteration to the peptide backbone conformation occurs with aza-glycine incorporation.