8GUU

Crystal structure of pilus-specific sortase C mutant from Streptococcus sanguinis

Summary for 8GUU

• Entry DOI: 10.2210/pdb8guu/pdb
• Related: 8GR6
• Descriptor: Sortase-like protein, putative, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: hydrolase, sortase c, pilus-specific sortase, cysteine transpeptidase, dental plaque, biofilm, pili
• Biological source: Streptococcus sanguinis SK36
• Total number of polymer chains: 1
• Total formula weight: 21812.57

Authors

Yadav, S.,Parijat, P. (deposition date: 2022-09-13, release date: 2023-06-21, Last modification date: 2023-11-29)

Primary citation

Yadav, S.,Parijat, P.,Krishnan, V.
Crystal structure of the pilus-specific sortase from early colonizing oral Streptococcus sanguinis captures an active open-lid conformation.
Int.J.Biol.Macromol., 243:125183-125183, 2023

PubMed 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.

PubMed: 37276901
DOI: 10.1016/j.ijbiomac.2023.125183

Experimental method

X-RAY DIFFRACTION (2.008 Å)