摘要
背景:肽聚糖是所有细菌细胞壁的重要组成部分。特别是革兰氏阳性菌的细胞壁主要由一层厚的肽聚糖组成。其可及性对其在整个细菌检测方法中的传感具有重要意义。事实上,迫切需要能够识别整个细菌的快速测试,例如在护理点直接进行。 目的:探讨结核分枝杆菌关键细胞分裂蛋白RipA对革兰氏阳性菌全细胞生物传感的适用性。 方法:我们进行分子动力学研究,旨在了解活性RipA的结构和动力学特征,并设计合适的生物受体。基于这些研究,我们设计了一种RipA变体,用于在黄金表面共价定向固定化,能够结合肽聚糖,尽管不会降解它。采用表面等离子体共振(SPR)技术检测功能化金片对整个细菌的识别能力。 结果:MD分析阐明了RipA活性形式的结构细节,提示该酶一旦失活,呈现出一个刚性的、暴露良好的肽聚糖识别裂缝。我们为SPR研究设计了RipA在黄金芯片上的适当定向固定。结果表明,一旦与黄金芯片化学偶联,开发的基于RipA的生物受体能够检测枯草芽孢杆菌,作为浓度依赖模式的模型。 结论:研究结果表明,该工程分子具有开发用于临床诊断或食源性感染的革兰氏阳性污染的早期预警生物传感器的潜力。
关键词: 蛋白质,肽聚糖,结构,结合,SPR, RipA。
Current Medicinal Chemistry
Title:Structural and Binding Properties of the Active Cell Wall Hydrolase RipA from M. tuberculosis, a Promising Biosensing Molecule for Early Warning Bacterial Detection
Volume: 29 Issue: 24
关键词: 蛋白质,肽聚糖,结构,结合,SPR, RipA。
摘要:
Background: Peptidoglycan is an essential component of the cell wall in all bacteria. In particular, the cell walls of Gram-positive bacteria are composed mostly of a thick layer of peptidoglycan. Its accessibility has important implications for their sensing in whole bacterial detection methodologies. Indeed, there is an urgent demand for rapid tests which can identify whole bacteria, e.g., directly at the point of care.
Objective: The aim of this work is to explore the suitability of RipA, a key cell division protein of M. tuberculosis, for whole cell biosensing of Gram-positive bacteria.
Methods: We here conducted Molecular Dynamics (MD) studies aimed at the understanding of the structural and dynamic features of active RipA and at the design of a suitable bioreceptor. Based on these studies, we engineered a RipA variant for covalent oriented immobilisation on golden surfaces and are able to bind peptidoglycan, albeit without degrading it. Surface Plasmon Resonance (SPR) was employed to check the ability of functionalized golden chips to recognize whole bacteria.
Results: MD analyses elucidated the structural details of the active form of RipA and suggested that this enzyme, once inactivated, presents a rigid and well-exposed peptidoglycan recognition cleft. We engineered RipA for proper oriented immobilisation on golden chips for SPR studies. Results show that once chemically coupled to a golden chip, the developed RipA-based bioreceptor is able to detect B. subtilis, used as a model in a concentration-dependent mode.
Conclusion: Results highlight the potential of the engineered molecule to be integrated in the development of early warning biosensors for Gram-positive contamination in clinical diagnosis or food-borne infections.
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Cite this article as:
Structural and Binding Properties of the Active Cell Wall Hydrolase RipA from M. tuberculosis, a Promising Biosensing Molecule for Early Warning Bacterial Detection, Current Medicinal Chemistry 2022; 29 (24) . https://dx.doi.org/10.2174/0929867329666220203115122
DOI https://dx.doi.org/10.2174/0929867329666220203115122 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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