Structural studies of Staphylococcus aureus Sortase inhibiton via Conus venom peptides.

Structural studies of Staphylococcus aureus Sortase inhibiton via Conus venom peptides. Arch Biochem Biophys. 2019 Jun 24;: Authors: Sameera SY, Rashid S Abstract Sortases (Srts) are transpeptidase enzymes that anchor plethora of surface proteins with LPXTG and NPQTN motifs to the cell wall of Gram-positive bacteria, and they are potential targets for the development of anti-infective agents. Despite the existence of numerous inhibitors for Staphylococcus aureus SrtA (SaSrtA), only two inhibitors are known for Staphylococcus aureus SrtB (SaSrtB). Moreover, no study has yet documented the anti-virulence potential of cone snail venom conopeptides against these virulence factors. Here we report M2-conotoxin and contryphan-R as effective inhibitory agents that may competitively block the binding of natural substrates with SaSrtA and SrtB, respectively, via molecular docking and dynamic simulation assays. M2-conotoxin also exhibited strong binding inside the catalytic grooves of distantly related SrtA homologs from Streptococcus mutans (SmSrtA) and Streptococcus agalactiae (SgSrtA). On the other hand, contryphan-R failed to occupy the substrate binding site of closely related Bacillus anthracis SrtB (BaSrtB), but successfully blocked the catalytic site of very divergent C. Perfringens SrtB (CpSrtB). Hence, these naturally existing venom peptides and their mimetics may serve as promising candidates for further development of therapeuticall...
Source: Archives of Biochemistry and Biophysics - Category: Biochemistry Authors: Tags: Arch Biochem Biophys Source Type: research