• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Coupling of calcium and substrate binding through loop alignment in the outer-membrane transporter BtuB.
【24h】

Coupling of calcium and substrate binding through loop alignment in the outer-membrane transporter BtuB.

机译：钙和底物结合的结合通过外膜转运蛋白BtuB中的环对齐来实现。

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

In Gram-negative bacteria, TonB-dependent outer-membrane transporters bind large, scarce organometallic substrates with high affinity preceding active transport. The cobalamin transporter BtuB requires the additional binding of two Ca(2+) ions before substrate binding can occur, but the underlying molecular mechanism is unknown. Using the crystallographic structures available for different bound states of BtuB, we have carried out extended molecular dynamics simulations of multiple functional states of BtuB to address the role of Ca(2+) in substrate recruitment. We find that Ca(2+) binding both stabilizes and repositions key extracellular loops of BtuB, optimizing interactions with the substrate. Interestingly, replacement by Mg(2+) abolishes this effect, in accordance with experiments. Using a set of new force-field parameters developed for cyanocobalamin, we also simulated the substrate-bound form of BtuB, where we observed interactions not seen in the crystal structure between the substrate and loops previously found to be important for binding and transport. Based on our results, we suggest that the large size of cobalamin compared to other TonB-dependent transporter substrates explains the requirement of Ca(2+) binding for high-affinity substrate recruitment in BtuB.
机译：在革兰氏阴性细菌中，依赖TonB的外膜转运蛋白在主动转运之前以高亲和力结合大而稀少的有机金属底物。钴胺素转运蛋白BtuB需要两个Ca（2+）离子的额外结合，然后才能发生底物结合，但潜在的分子机制尚不清楚。使用可用于BtuB的不同结合状态的晶体结构，我们进行了BtuB多个功能状态的扩展的分子动力学模拟，以解决Ca（2+）在底物募集中的作用。我们发现Ca（2+）结合稳定和重新定位BtuB的关键细胞外环，优化与底物的相互作用。有趣的是，根据实验，用Mg（2+）替代可以消除这种效应。使用为氰钴胺素开发的一组新的力场参数，我们还模拟了BtuB的底物结合形式，在其中我们观察到了底物与先前发现对结合和运输很重要的环之间的晶体结构中未发现的相互作用。根据我们的结果，我们建议与其他TonB依赖性转运蛋白底物相比，钴胺素的尺寸较大，这说明Ca（2+）结合对于BtuB中高亲和力底物募集的要求。

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