An RNA aptamer exploits exosite-dependent allostery to achieve specific inhibition of coagulation factor IXa.

ABSTRACT: Hemostasis relies on a reaction network of serine proteases and their cofactors to form a blood clot. Coagulation factor IXa (protease) plays an essential role in hemostasis as evident from the bleeding disease associated with its absence. RNA aptamers specifically targeting individual coagulation factors have potential as anticoagulants and as probes of the relationship between structure and function. Here, we report X-ray structures of human factor IXa without a ligand bound to the active site either in the apo-form or in complex with an inhibitory aptamer specific for factor IXa. The aptamer binds to an exosite in the catalytic domain and allosterically distorts the active site. Our studies reveal a conformational ensemble of IXa states, wherein large movements of Trp₂₁₅ near

SUBMITTER: Kolyadko VN 

PROVIDER: S-EPMC11260126 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature