Single fluorescence probes along the reactive center loop reveal site-specific changes during the latency transition of PAI-1.

ABSTRACT: The serine protease inhibitor (serpin), plasminogen activator inhibitor-1 (PAI-1), is an important biomarker for cardiovascular disease and many cancers. It is therefore a desirable target for pharmaceutical intervention. However, to date, no PAI-1 inhibitor has successfully reached clinical trial, indicating the necessity to learn more about the mechanics of the serpin. Although its kinetics of inhibition have been extensively studied, less is known about the latency transition of PAI-1, in which the solvent-exposed reactive center loop (RCL) inserts into its central β-sheet, rendering the inhibitor inactive. This spontaneous transition is concomitant with a large translocation of the RCL, but no change in covalent structure. Here, we conjugated the fluorescent probe, NBD, to single posit

SUBMITTER: Qureshi T 

PROVIDER: S-EPMC4815349 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature