Crystal structure of the antimicrobial peptidase lysostaphin from Staphylococcus simulans

Sabala, Izabela; Jagielska, Elzbieta; Bardelang, Philip T.; Czapinska, Honorata; Dahms, Sven O.; Sharpe, Jason A.; James, Richard; Than, Manuel E.; Thomas, Neil R.; Bochtler, Matthias

Abstract

Staphylococcus simulansbiovarstaphylolyticuslysostaphin efficiently cleavesStaphylococcus aureuscell walls. The protein is in late clinical trials as atopical anti-staphylococcal agent, and can be used to prevent staphylococcalgrowth on artificial surfaces. Moreover, the gene has been both stably engi-neered into and virally delivered to mice or livestock to obtain resistanceagainst staphylococci. Here, we report the first crystal structure of maturelysostaphin and two structures of its isolated catalytic domain at 3.5, 1.78and 1.26A resolution, respectively. The structure of the mature activeenzyme confirms its expected organization into catalytic and cell-wall-targeting domains. It also indicates that the domains are mobile with respectto each other because of the presence of a highly flexible peptide linker. Thehigh-resolution structures of the catalytic domain provide details of Zn2+coordination and may serve as a starting point for the engineering of lyso-staphin variants with improved biotechnological characteristics.

• Journal Article Type: Article
• Acceptance Date: Jul 11, 2014
• Publication Date: Sep 1, 2014
• Deposit Date: Feb 22, 2018
• Publicly Available Date: Apr 11, 2019
• Print ISSN: 1742-464X
• Electronic ISSN: 1742-4658
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 281
• Issue: 18
• Pages: 4112-4122
• DOI: https://doi.org/10.1111/febs.12929
• Public URL: https://nottingham-repository.worktribe.com/output/1107351
• Publisher URL: https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.12929
• PMID: 00034258