Mapping the Mutational Landscape for Streptokinase Binding to Plasminogen.

ABSTRACT: Group A Streptococcus (GAS) expresses streptokinase (SK), a critical virulence factor that non-enzymatically activates the host's plasminogen (PLG), to an active form, PLG _SK , resulting in the degradation of fibrin clots and subsequent bacterial dissemination. PLG _SK formation contrasts with the physiologic activation of PLG to the serine protease plasmin via a proteolytic mechanism. As a potent thrombolytic, SK has been used as a therapeutic to treat heart attacks and strokes. GAS SK is highly specific for human PLG, and sequence variation between SK from different GAS strains has been linked to differences in PLG binding and disease severity. We now report the application of deep mutational scanning (DMS) to map the effects of ∼71% of single amino acid substitution

SUBMITTER: Baid S 

PROVIDER: S-EPMC12893055 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature