Protease mimicry: Dissecting the ester bond crosslinking mechanics in bacterial adhesin proteins.

ABSTRACT: The ester bond crosslink discovered within bacterial adhesin proteins offers a captivating insight into the convergent evolution of enzyme-like machinery. Crystal structures reveal a putative catalytic triad comprising an acid-base-nucleophile combination and an oxyanion-like site that suggests a serine protease-like mechanism drives the crosslinking process. We now provide confirmation of the mechanism, revealing functional catalytic dyads or triads, and the recapitulation of protease machinery from a Pseudomonas bacterium and a human cytomegalovirus related only by convergent evolution. Molecular dynamics simulations suggest how a conservative threonine-to-serine mutation of the nucleophile induces hydrolysis and eliminates the ester bond crosslink. Collectively, our structural, function

SUBMITTER: Yosaatmadja Y 

PROVIDER: S-EPMC12679949 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature