NMR reveals a dynamic allosteric pathway in thrombin.

ABSTRACT: Although serine proteases are found ubiquitously in both eukaryotes and prokaryotes, and they comprise the largest of all of the peptidase families, their dynamic motions remain obscure. The backbone dynamics of the coagulation serine protease, apo-thrombin (S195M-thrombin), were compared to the substrate-bound form (PPACK-thrombin). R₁, R₂, ¹⁵N-{¹H}NOEs, and relaxation dispersion NMR experiments were measured to capture motions across the ps to ms timescale. The ps-ns motions were not significantly altered upon substrate binding. The relaxation dispersion data revealed that apo-thrombin is highly dynamic, with μs-ms motions throughout the molecule. The region around the N-terminus of the heavy chain, the Na⁺-binding loop, and the 170 

SUBMITTER: Handley LD 

PROVIDER: S-EPMC5216386 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature