Interactions of substrates and phosphinyl containing inhibitors with bacterial and human zinc proteases.

ABSTRACT: Inhibitors of bacterial virulence is suggested to be a promising strategy in the fight against bacterial resistance. The zinc metalloproteases (MPs) thermolysin (TLN), pseudolysin (PLN, LasB) and aureolysin (ALN) are bacterial virulence factors from the M4 family of proteases structurally resembling human zinc MPs. Knowledge about the binding modes of substrates and inhibitors with the bacterial and human zinc MPs is therefore fundamental for developing inhibitors without strong off-target effects. In the present paper, we studied the molecular interactions and cleavage of TLN, the prototype enzyme of the M4 family, with the substrate Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(Dnp)-OH (ES005) by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and mo

SUBMITTER: Rahman FA 

PROVIDER: S-EPMC12316308 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature