...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Acta crystallographica. Section D, Structural biology >Structure of the N-terminal domain of ClpC1 in complex with the antituberculosis natural product ecumicin reveals unique binding interactions
【24h】

Structure of the N-terminal domain of ClpC1 in complex with the antituberculosis natural product ecumicin reveals unique binding interactions

机译：ClpC1的n端结构域的结构复杂的公开的天然产品ecumicin揭示独特的绑定交互

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

The biological processes related to protein homeostasis in Mycobacterium tuberculosis, the etiologic agent of tuberculosis, have recently been established as critical pathways for therapeutic intervention. Proteins of particular interest are ClpCl and the ClpCl-ClpPl-ClpP2 proteasome complex. The structure of the potent antituberculosis macrocyclic depsipeptide ecumicin complexed with the N-terminal domain of ClpCl (ClpCl-NTD) is presented here. Crystals of the ClpCl-NTD-ecumicin complex were monoclinic (unit-cell parameters a = 80.0, b = 130.0, c = 112.0 A, β= 90.07°; space group P2_1; 12 complexes per asymmetric unit) and diffracted to 2.5 A resolution. The structure was solved by molecular replacement using the self-rotation function to resolve space-group ambiguities. The new structure of the ecumicin complex showed a unique 1:2 (target:ligand) stoichiometry exploiting the intramolecular dyad in the α-helical fold of the target N-terminal domain. The structure of the ecumicin complex unveiled extensive interactions in the uniquely extended N-terminus, a critical binding site for the known cyclopeptide complexes. This structure, in comparison with the previously reported rufomycin I complex, revealed unique features that could be relevant for understanding the mechanism of action of these potential antituberculosis drug leads. Comparison of the ecumicin complex and the ClpCl-NTD-L92S/L96P double-mutant structure with the available structures of rufomycin I and cyclomarin A complexes revealed a range of conformational changes available to this small N-terminal helical domain and the minor helical alterations involved in the antibiotic-resistance mechanism. The different modes of binding and structural alterations could be related to distinct modes of action.
机译：相关的生物过程的蛋白质结核分枝杆菌的体内平衡最近结核病的病原体建立了关键路径治疗性干预。兴趣是ClpCl ClpCl-ClpPl-ClpP2蛋白酶体复杂。对公开大环的depsipeptideecumicin复杂化的n端结构域下面是ClpCl (ClpCl-NTD)。单斜ClpCl-NTD-ecumicin复杂(晶胞参数= 80.0,b = 130.0, c =112.0,β= 90.07°;每个不对称单位)和衍射复合物2.5一项决议。分子替换使用固有转动函数来解决空间群模棱两可。新结构的ecumicin复杂的显示独特的1:2(目标:配体)化学计量学利用分子内二分体的α螺旋折叠目标n端结构域。ecumicin的结构复杂的了广泛的相互作用的独特的扩展n端,一个关键的结合位点环肽复合物。与以前相比rufomycin报道我复杂,显示独特的特性理解的机制有关行动公开这些潜在的药物线索。ClpCl-NTD-L92S / L96P double-mutant结构可用rufomycin我和结构cyclomarin复合物显示范围这个小构象变化氨基端螺旋域和小螺旋改变参与病人机制。结构的改变可能与不同的行动模式。

著录项

相似文献

  • 外文文献
  • 中文文献
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