Structural insights into the role of the N‐terminus in the activation and function of extracellular serine protease from Staphylococcus epidermidis. Issue 1 (2nd January 2020)

• Record Type: Journal Article
• Authors: Manne, Kartik; Narayana, Sthanam V. L.
• Is Part Of: Acta crystallographica. Volume 76:Issue 1(2020)
• Page Start: 28
• Page End: 40
• Publication Date: 2020-01-02
• Subjects: extracellular serine protease -- glutamyl endopeptidase -- zymogen -- crystal structure -- Staphylococcus epidermidis; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; Molecular biology -- Periodicals; Molecular structure -- Periodicals; Biomolecules -- Structure -- Periodicals; Cytology -- Periodicals; Biomolecules -- Structure; Crystallography; Cytology; Molecular biology; Molecular structure; X-ray crystallography; Periodicals; 548
• DOI: 10.1107/S2059798319015055
• Languages: English
• ISSNs: 2059-7983

Abstract

Abstract : Extracellular serine protease (Esp) is a glutamyl endopeptidase from Staphylococcus epidermidis that plays a key role in inhibiting the growth and formation of Staphylococcus aureus biofilms. Here, crystal structures of the Esp zymogen and its N‐terminal locked variants are presented, and details are given of the role of the unusually long N‐terminus in the activation and function of Esp. Abstract : Extracellular serine protease (Esp) from Staphylococcus epidermidis is a glutamyl endopeptidase that inhibits the growth and formation of S. aureus biofilms. Previously, crystal structures of the matured and active Esp have been determined. Interestingly, many of the staphylococcal glutamyl endopeptidase zymogens, including V8 from Staphylococcus aureus and Esp from S. epidermidis, contain unusually long pro‐peptide segments; however, their function is not known. With the aim of elucidating the function of these pro‐peptide segments, crystal structures of the Esp zymogen (Pro‐Esp) and its variants were determined. It was observed that the N‐terminus of the Pro‐Esp crystal structure is flexible and is not associated with the main body of the enzyme, unlike in the known active Esp structure. In addition, the loops that border the putative substrate‐binding pocket of Pro‐Esp are flexible and disordered; the structural components that are responsible for enzyme specificity and efficiency in serine proteases are disordered in Pro‐Esp. However, the N‐terminal locked Pro‐Esp variants exhibit a rigid substrate‐binding pocket similar to the active Esp structure and regain activity. These structural studies highlight the role of the N‐terminus in stabilizing the structural components responsible for the activity and specificity of staphylococcal glutamyl endopeptidases.