Unknown

Dataset Information

0

Latency, thermal stability, and identification of an inhibitory compound of mirolysin, a secretory protease of the human periodontopathogen Tannerella forsythia.


ABSTRACT: Mirolysin is a secretory protease of Tannerella forsythia, a member of the dysbiotic oral microbiota responsible for periodontitis. In this study, we show that mirolysin latency is achieved by a "cysteine-switch" mechanism exerted by Cys23 in the N-terminal profragment. Mutation of Cys23 shortened the time needed for activation of the zymogen from several days to 5 min. The mutation also decreased the thermal stability and autoproteolysis resistance of promirolysin. Mature mirolysin is a thermophilic enzyme and shows optimal activity at 65 °C. Through NMR-based fragment screening, we identified a small molecule (compound (cpd) 9) that blocks promirolysin maturation and functions as a competitive inhibitor (Ki = 3.2 µM), binding to the S1' subsite of the substrate-binding pocket. Cpd 9 shows superior specificity and does not interact with other T. forsythia proteases or Lys/Arg-specific proteases.

SUBMITTER: Zak KM 

PROVIDER: S-EPMC8259862 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4682893 | biostudies-literature
| S-EPMC2934765 | biostudies-literature
| PRJDB2011 | ENA
| PRJNA35201 | ENA
| S-EPMC4281766 | biostudies-literature
| S-EPMC8550257 | biostudies-literature
| S-EPMC7014623 | biostudies-literature
| PRJDB1007 | ENA
| PRJDB1008 | ENA
| PRJNA319 | ENA