Remodeling of Cross-bridges Controls Peptidoglycan Cross-linking Levels in Bacterial Cell Walls.,ACS Chemical Biology

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Remodeling of Cross-bridges Controls Peptidoglycan Cross-linking Levels in Bacterial Cell Walls.
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2020-04-03 , DOI: 10.1021/acschembio.0c00002
Alexis J Apostolos ₁ , Sean E Pidgeon ₁ , Marcos M Pires ₁

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Cell walls are barriers found in almost all known bacterial cells. These structures establish a controlled interface between the external environment and vital cellular components. A primary component of cell wall is a highly cross-linked matrix called peptidoglycan (PG). PG cross-linking, carried out by transglycosylases and transpeptidases, is necessary for proper cell wall assembly. Transpeptidases, targets of β-lactam antibiotics, stitch together two neighboring PG stem peptides (acyl-donor and acyl-acceptor strands). We recently described a novel class of cellular PG probes that were processed exclusively as acyl-donor strands. Herein, we have accessed the other half of the transpeptidase reaction by developing probes that are processed exclusively as acyl-acceptor strands. The critical nature of the cross-bridge on the PG peptide was demonstrated in live bacterial cells, and surprising promiscuity in cross-bridge primary sequence was found in various bacterial species. Additionally, acyl-acceptor probes provided insight into how chemical remodeling of the PG cross-bridge (e.g., amidation) can modulate cross-linking levels, thus establishing a physiological role of PG structural variations. Together, the acyl-donor and -acceptor probes will provide a versatile platform to interrogate PG cross-linking in physiologically relevant settings.

中文翻译：

跨桥的重塑控制细菌细胞壁中的肽聚糖交联水平。

细胞壁是几乎所有已知细菌细胞中发现的屏障。这些结构在外部环境和重要的细胞成分之间建立了受控的接口。细胞壁的主要成分是称为肽聚糖（PG）的高度交联的基质。通过转糖基化酶和转肽酶进行的PG交联对于正确的细胞壁组装是必需的。作为β-内酰胺抗生素的靶标的转肽酶将两条相邻的PG干肽（酰基供体和酰基受体链）缝合在一起。我们最近描述了一类新型的细胞PG探针，仅被加工成酰基供体链。在本文中，我们通过开发仅作为酰基受体链加工的探针来获得转肽酶反应的另一半。PG肽上的跨桥的关键性质已在活细菌细胞中得到证实，并且在各种细菌物种中发现了跨桥一级序列令人惊讶的混杂。此外，酰基受体探针提供了对PG跨桥化学重塑（例如酰胺化）如何调节交联水平的见解，从而确立了PG结构变化的生理作用。酰基供体探针和受体受体一起将提供一个多功能平台，用于在生理相关环境中询问PG交联。酰胺化）可以调节交联水平，从而建立PG结构变化的生理作用。一起，酰基供体和-受体探针将提供一个通用的平台，以在生理相关的环境中询问PG交联。酰胺化）可以调节交联水平，从而建立PG结构变化的生理作用。一起，酰基供体和-受体探针将提供一个通用的平台，以在生理相关的环境中询问PG交联。

更新日期：2020-03-13

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