Department of Chemistry, Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL, 61801, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
J Ind Microbiol Biotechnol. 2019 Mar;46(3-4):537-549. doi: 10.1007/s10295-018-2110-9. Epub 2018 Nov 27.
CylA is a subtilisin-like protein belonging to a recently expanded serine protease family related to class II lanthipeptide biosynthesis. As a leader peptidase, CylA is responsible for maturation of the enterococcal cytolysin, a lantibiotic important for Enterococcus faecalis virulence. In vitro reconstitution of CylA reveals that it accepts both linear and modified cytolysin peptides with a preference for cyclized peptides. Further characterization indicates that CylA activates itself by removing its N-terminal 95 amino acids. CylA achieves sequence-specific traceless cleavage of non-cognate peptides even if they are post-translationally modified, which makes the peptidase a powerful tool for mining novel lanthipeptides by providing a general strategy for leader peptide removal. Knowledge about the substrate specificity of CylA may also facilitate the development of protease inhibitors targeting cytolysin biosynthesis as a potential therapeutic approach for enterococcal infections.
CylA 是一种枯草溶菌素样蛋白，属于最近扩展的丝氨酸蛋白酶家族，与 II 类兰尼丁肽生物合成有关。作为一个启动肽酶，CylA 负责肠球菌细胞溶素的成熟，该兰尼丁肽对粪肠球菌的毒力很重要。体外重建 CylA 表明，它接受线性和修饰的细胞溶素肽，偏爱环化肽。进一步的特征表明，CylA 通过去除其 N 端的 95 个氨基酸来激活自身。CylA 可以对非同源肽进行序列特异性无痕切割，即使它们是经过翻译后修饰的，这使得该肽酶成为通过提供一种通用的启动肽去除策略来挖掘新型兰尼丁肽的有力工具。对 CylA 的底物特异性的了解也可能有助于开发针对细胞溶素生物合成的蛋白酶抑制剂，作为肠球菌感染的一种潜在治疗方法。
