Development of selective protease inhibitors via engineering of the bait region of human α₂-macroglobulin.

ABSTRACT: Human α₂-macroglobulin (A2M) is an abundant protease inhibitor in plasma, which regulates many proteolytic processes and is involved in innate immunity. A2M's unique protease-trapping mechanism of inhibition is initiated when a protease cleaves within the exposed and highly susceptible "bait region." As the wild-type bait region is permissive to cleavage by most human proteases, A2M is accordingly a broad-spectrum protease inhibitor. In this study, we extensively modified the bait region in order to identify any potential functionally important elements in the bait region sequence and to engineer A2M proteins with restrictive bait regions, which more selectively inhibit a target protease. A2M in which the bait region was entirely replaced by glycine-serine repeats remained fully

SUBMITTER: Harwood SL 

PROVIDER: S-EPMC8267569 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature