...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Selenoglutathione: Efficient Oxidative Protein Folding by a Diselenide
【24h】

Selenoglutathione: Efficient Oxidative Protein Folding by a Diselenide

机译：硒代谷胱甘肽：二硒化物的有效氧化蛋白折叠。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Diselenide bonds are intrinsically more stable than disulfide bonds. To examine how this stability difference affects reactivity, we synthesized selenoglutathione (GSeSeG), an analogue of the oxidized form of the tripeptide glutathione that contains a diselenide bond in place of the natural disulfide. The reduction potential of this diselenide bond was determined to be -407 ± 9 mV, a value which is 151 mV lower than that of the disulfide bond in glutathione (GSSG). Thus, the diselenide bond of GSeSeG is 7 kcal/mol more stable than the disulfide bond of GSSG. Nonetheless, we found that GSeSeG can be used to oxidize cysteine residues in unfolded proteins, a process that is driven by the gain in protein conformational stability upon folding. Indeed, the folding of both ribonuclease A (RNase A) and bovine pancreatic trypsin inhibitor (BPTI) proceeded efficiently using GSeSeG as an oxidant, in the former case with a 2-fold rate increase relative to GSSG and in the latter case accelerating conversion of a stable folding intermediate to the native state. In addition, GSeSeG can also oxidize the common biological cofactor NADPH and is a good substrate for the NADPH-dependent enzyme glutathione reductase (k_(cat) - 69 ± 2 s~(_1), K_m = 54 ± 7 mu M), suggesting that diselenides can efficiently interact with the cellular redox machinery. Surprisingly, the greater thermodynamic stability of diselenide bonds relative to disulfide bonds is not matched by a corresponding decrease in reactivity.
机译：二硒键本质上比二硫键稳定。为了检查这种稳定性差异如何影响反应性，我们合成了硒代谷胱甘肽（GSeSeG），它是三肽谷胱甘肽的氧化形式的类似物，其中含有二硒键而不是天然的二硫键。确定该二硒键的还原电位为-407±9mV，该值比谷胱甘肽（GSSG）中的二硫键的还原电位低151mV。因此，GSeSeG的二硒键比GSSG的二硫键稳定7kcal / mol。尽管如此，我们发现GSeSeG可用于氧化未折叠蛋白质中的半胱氨酸残基，该过程由折叠时蛋白质构象稳定性的提高驱动。确实，使用GSeSeG作为氧化剂，核糖核酸酶A（RNase A）和牛胰胰蛋白酶抑制剂（BPTI）的折叠均有效进行，在前一种情况下，其相对于GSSG的速率增加了2倍，而在后一种情况下，加速了GSSG的转化。在原始状态下稳定的折叠状态。此外，GSeSeG还可以氧化常见的生物辅因子NADPH，并且是NADPH依赖性酶谷胱甘肽还原酶（k_（cat）-69±2 s〜（_1），K_m = 54±7μM）的良好底物，表明二硒化物可以有效地与细胞氧化还原机制相互作用。令人惊讶地，二硒键相对于二硫键的更大的热力学稳定性与反应性的相应降低不匹配。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号