Exploring the Competence Stimulating Peptide (CSP) N-terminal Requirements for Effective ComD Receptor Activation in Group1 Streptococcus pneumoniae
Exploring the Competence Stimulating Peptide (CSP) N-terminal Requirements for Effective ComD Receptor Activation in Group1 Streptococcus pneumoniae
复制标题
探索 1 组肺炎链球菌有效激活 ComD 受体的能力刺激肽 (CSP) N 端要求
DOI：
10.1016/j.bioorg.2019.102987
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发表时间：
2019
影响因子：
5.1
通讯作者：
Tal-Gan, Yftah
中科院分区：
文献类型：
--
作者：
Yang, Yifang;Tal-Gan, Yftah
感受态刺激肽（CSP）在调节肺炎球菌群体感应（QS）中起关键作用，QS是肺炎球菌感染性的关键通讯系统。CSP通过结合和激活跨膜受体ComD发挥作用。能够通过阻断CSP：ComD相互作用来调节肺炎球菌QS的分子可能作为新一代治疗肺炎球菌感染的抗菌剂。在这项工作中，我们系统地修改了CSP 1的N-末端，这是一个对ComD激活至关重要的区域，以确定负责其功能的N-末端的详细结构特征。我们的研究结果揭示了实现受体活化的最佳结构特征和结构-活性趋势，提高了我们对CSP：ComD相互作用的理解，所有这些都将有助于设计具有更高效力和改善药理学性质的新型肺炎球菌QS调节剂。
The competence stimulating peptide (CSP) plays a key role in the regulation of pneumococcal quorum sensing (QS), a communication system that is critical to the infectivity of pneumococci. CSP functions through binding and activating a transmembrane receptor, ComD. Molecules that can modulate pneumococcal QS through intercepting CSP:ComD interaction may serve as new generation of antibacterial agents to treat pneumococcal infections. In this work, we systematically modified theN-terminus of CSP1, a region that is essential to ComD activation, to identify detailed structural features of theN-terminus that are responsible for its function. Our results revealed structural features that are optimal to achieve receptor activation and structure-activity trends that improve our understanding of CSP:ComD interaction, all of which will contribute to the design of novel pneumococcal QS modulators with higher potency and improved pharmacological properties.