Publication: Molecular insights into Zn<sup>2+</sup> inhibition of the antibacterial endopeptidase lysostaphin from Staphylococcus simulans
Issued Date
2021-01-01
Resource Type
ISSN
18755305
09298665
09298665
Other identifier(s)
2-s2.0-85103744719
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Mahidol University
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SCOPUS
Bibliographic Citation
Protein and Peptide Letters. Vol.28, No.2 (2021), 20-28
Suggested Citation
Ke Chen, Suvash Chandra Ojha, Chompounoot Imtong, Aung Khine Linn, Hui Chun Li, Charoensri Thonabulsombat, Chanan Angsuthanasombat Molecular insights into Zn<sup>2+</sup> inhibition of the antibacterial endopeptidase lysostaphin from Staphylococcus simulans. Protein and Peptide Letters. Vol.28, No.2 (2021), 20-28. doi:10.2174/0929866527666200613221359 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/76389
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Title
Molecular insights into Zn<sup>2+</sup> inhibition of the antibacterial endopeptidase lysostaphin from Staphylococcus simulans
Abstract
Background: Mature lysostaphin (~28-kDa Lss) from Staphylococcus simulans proves effective in killing methicillin-resistant Staphylococcus aureus (MRSA) which is endemic in hospitals worldwide. Lss is Zn2+-dependent endopeptidase, but its bacteriolytic activity could be affected by exogenously added Zn2+. Objective: To gain greater insights into structural and functional impacts of Zn2+and Ni2+on Lss-induced bioactivity. Methods: Lss purified via immobilized metal ion-affinity chromatography was assessed for bioactivity using turbidity reduction assays. Conformational change of metal ion-treated Lss was examined by circular dichroism and intrinsic fluorescence spectroscopy. Co-sedimentation assay was performed to study interactions between Zn2+-treated Lss and S. aureus peptidoglycans. Metal ionbinding prediction and intermolecular docking were used to locate an extraneous Zn2+-binding site. Results: A drastic decrease in Lss bioactivity against S. aureus and MRSA was revealed only when treated with Zn2+, but not Ni2+, albeit no negative effect of diethyldithiocarbamate-Zn2+-chelator on Lss-induced bioactivity. No severe conformational change was observed for Lss incubated with exogenous Zn2+ or Ni2+. Lss pre-treated with Zn2+ efficiently bound to S. aureus cell-wall peptidoglycans, suggesting non-interfering effect of exogenous metal ions on cell-wall targeting (CWT) activity. In silico analysis revealed that exogenous Zn2+, but not Ni2+, preferably interacted with a potential extraneous Zn2+-binding site (His253, Glu318 and His323) placed near the Zn2+-coordinating Lssactive site within the catalytic (CAT) domain. Conclusion: Our present data signify the adverse influence of exogenous Zn2+ ions on Lss-induced staphylolytic activity through the exclusive presence within the CAT domain of an extraneous inhibitory Zn2+-binding site, without affecting the CWT activity.