Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae.
Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae.
复制标题
DOI：
10.3762/bjoc.14.151
复制
发表时间：
2018
影响因子：
2.7
通讯作者：
Tal-Gan Y
中科院分区：
文献类型：
--
作者：
Koirala B;Hillman RA;Tiwold EK;Bertucci MA;Tal-Gan Y
群体感应（QS）是一种细胞间通讯机制，使细菌能够评估其种群密度并在达到高细胞数时改变其行为。许多细菌病原体利用QS来启动对其宿主的攻击，因此QS作为传统抗生素的潜在抗毒力替代品引起了极大的关注。肺炎链球菌（Streptococcus pneumoniae）是一种引起多种急性和慢性感染的臭名昭著的人类病原体，其利用感受态调节子及其相关的信号肽（感受态刺激肽（CSP））获得抗生素抗性并建立感染。在这项工作中，我们试图通过在肽内引入高度保守的点突变来定义用于结合CSP 1中疏水侧链残基的ComD1受体内的结合口袋。这些结合相互作用的优化可能导致开发高效的基于CSP的QS调节剂，而在CSP序列内包含非天然氨基酸将赋予对蛋白酶降解的抗性，这是候选药物的要求。
Quorum sensing (QS) is a cell–cell communication mechanism that enables bacteria to assess their population density and alter their behavior upon reaching high cell number. Many bacterial pathogens utilize QS to initiate an attack on their host, thus QS has attracted significant attention as a potential antivirulence alternative to traditional antibiotics. Streptococcus pneumoniae, a notorious human pathogen responsible for a variety of acute and chronic infections, utilizes the competence regulon and its associated signaling peptide, the competence stimulating peptide (CSP), to acquire antibiotic resistance and establish an infection. In this work, we sought to define the binding pockets within the ComD1 receptor used for binding the hydrophobic side-chain residues in CSP1 through the introduction of highly-conservative point mutations within the peptide. Optimization of these binding interactions could lead to the development of highly potent CSP-based QS modulators while the inclusion of non-natural amino acids within the CSP sequence would confer resistance to protease degradation, a requirement for drug candidates.
登录
查看更多内容
影响因子：
8.6
作者：
Wang B;Muir TW
通讯作者：
Muir TW
影响因子：
15
作者：
Tal-Gan Y;Ivancic M;Cornilescu G;Cornilescu CC;Blackwell HE
通讯作者：
Blackwell HE
DOI：
10.1002/anie.201602974
发表时间：
2016-07-25
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Tal-Gan Y;Ivancic M;Cornilescu G;Yang T;Blackwell HE
通讯作者：
Blackwell HE
影响因子：
15
作者：
Tal-Gan, Yftah;Stacy, Danielle M.;Blackwell, Helen E.
通讯作者：
Blackwell, Helen E.
影响因子：
3.6
作者：
Pestova, EV;Havarstein, LS;Morrison, DA
通讯作者：
Morrison, DA