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Crystal structure of the pilus-specific sortase from early colonizing oral Streptococcus sanguinis captures an active open-lid conformation.
- Source :
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International Journal of Biological Macromolecules . Jul2023, Vol. 243, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
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Abstract
- Dental plaque is a complex microbial biofilm community of many species and a major cause of oral infections and infectious endocarditis. Plaque development begins when primary colonizers attach to oral tissues and undergo coaggregation. Primary colonizers facilitate cellular attachment and inter-bacterial interactions through sortase-dependent pili (or fimbriae) extending out from their cell surface. Consequently, the sortase enzyme is viewed as a potential drug target for controlling biofilm formation and avoiding infection. Streptococcus sanguinis is a primary colonizing bacterium whose pili consist of three different pilin subunits that are assembled together by the pilus-specific (C-type) SsaSrtC sortase. Here, we report on the crystal structure determination of the recombinant wild-type and active-site mutant forms of SsaSrtC. Interestingly, the SsaSrtC structure exhibits an open-lid conformation, although a conserved DPX motif is lacking in the lid. Based on molecular docking and structural analysis, we identified the substrate-binding residues essential for pilin recognition and pilus assembly. We also demonstrated that while recombinant SsaSrtC is enzymatically active toward the five-residue LPNTG sorting motif peptide of the pilins, this activity is significantly reduced by the presence of zinc. We further showed that rutin and α-crocin are potential candidate inhibitors of the SsaSrtC sortase via structure-based virtual screening and inhibition assays. The structural knowledge gained from our study will provide the means to develop new approaches that target pilus-mediated attachment, thereby preventing oral biofilm growth and infection. • C-type sortase from S. sanguinis , an early colonizer of dental plaque, was produced, purified, and crystallized. • Crystal structure of SsaSrtC shows an open-lid conformation in the absence of a lid motif. • SsaSrtC activity toward pilin sorting motif involved in pilus assembly was demonstrated but is readily diminished by zinc. • Substrate-binding residues in the active site cleft of SsaSrtC were identified. • Rutin and α-crocin are potential candidate inhibitors of the SsaSrtC sortase. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01418130
- Volume :
- 243
- Database :
- Academic Search Index
- Journal :
- International Journal of Biological Macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 164345381
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2023.125183