Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b.,Nature Chemical Biology

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Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b.
Nature Chemical Biology ( IF 12.9 ) Pub Date : 2019-11-04 , DOI: 10.1038/s41589-019-0393-4
Luz S Gonzalez-Delgado _{1,

2} , Hannah Walters-Morgan ₃ , Bartłomiej Salamaga _{1,

2} , Angus J Robertson _{1,

2} , Andrea M Hounslow _{1,

2} , Elżbieta Jagielska ₄ , Izabela Sabała ₄ , Mike P Williamson _{1,

2} , Andrew L Lovering ₃ , Stéphane Mesnage _{1,

2}

Affiliation

Lysostaphin is a bacteriolytic enzyme targeting peptidoglycan, the essential component of the bacterial cell envelope. It displays a very potent and specific activity toward staphylococci, including methicillin-resistant Staphylococcus aureus. Lysostaphin causes rapid cell lysis and disrupts biofilms, and is therefore a therapeutic agent of choice to eradicate staphylococcal infections. The C-terminal SH3b domain of lysostaphin recognizes peptidoglycans containing a pentaglycine crossbridge and has been proposed to drive the preferential digestion of staphylococcal cell walls. Here we elucidate the molecular mechanism underpinning recognition of staphylococcal peptidoglycan by the lysostaphin SH3b domain. We show that the pentaglycine crossbridge and the peptide stem are recognized by two independent binding sites located on opposite sides of the SH3b domain, thereby inducing a clustering of SH3b domains. We propose that this unusual binding mechanism allows synergistic and structurally dynamic recognition of S. aureus peptidoglycan and underpins the potent bacteriolytic activity of this enzyme.

中文翻译：

溶葡萄球菌素 SH3b 对金黄色葡萄球菌肽聚糖的双位点识别。

溶葡萄球菌素是一种靶向肽聚糖的溶菌酶，肽聚糖是细菌细胞包膜的基本成分。它对葡萄球菌（包括耐甲氧西林的金黄色葡萄球菌）显示出非常有效的特异性活性。溶葡萄球菌素导致细胞快速裂解并破坏生物膜，因此是根除葡萄球菌感染的首选治疗剂。溶葡萄球菌素的 C 端 SH3b 结构域可识别含有五甘氨酸横桥的肽聚糖，并已被提议用于驱动葡萄球菌细胞壁的优先消化。在这里，我们阐明了支持溶葡萄球菌素 SH3b 结构域识别葡萄球菌肽聚糖的分子机制。我们表明，位于 SH3b 域两侧的两个独立结合位点可识别五甘氨酸桥和肽茎，从而诱导 SH3b 域的聚集。我们建议这种不寻常的结合机制允许对金黄色葡萄球菌肽聚糖的协同和结构动态识别，并支持这种酶的有效溶菌活性。

更新日期：2019-11-04

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