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From Loop To Strand: Characterization Of The Conformation And Dynamics Of The Human Plasminogen Activator Inhibitor-1 Reactive Center, Tihami Qureshi
From Loop To Strand: Characterization Of The Conformation And Dynamics Of The Human Plasminogen Activator Inhibitor-1 Reactive Center, Tihami Qureshi
Doctoral Dissertations
Plasminogen activator inhibitor-1 (PAI-1), with its cofactor vitronectin (VN), controls the rate of plasmin-mediated fibrin breakdown in blood clots by inhibiting tissue-plasminogen activator (tPA) and urokinase-plasminogen activator (uPA). The activity of PAI-1 is attributed to its reactive center loop (RCL), which is solvent-exposed in an active conformation, but inserts as an additional strand into its central β [beta]-sheet during transition to a latent state and during inhibition. VN slows the latency transition, and the rate at which PAI-1 inhibits the plasminogen activators (PAs) also differs. However, the steps during the latency transition, mechanism of VN stabilization, and basis for inhibitory …