Molecular Insights into the Intrinsic Dynamics and Their Roles During Catalysis in Pin1 Peptidyl-prolyl Isomerase

Mori, Toshifumi, Saito, Shinji

Proteins are intrinsically dynamic and change conformations over a wide range of time scales. While the conformational dynamics have been realized to be important for protein functions, e.g., in activity–stability trade-offs, how they play a role during enzyme catalysis has been of debate over decades. By studying Pin1 peptidyl-prolyl isomerase using extensive molecular dynamics simulations, here we discuss how the slow intrinsic dynamics of Pin1 observed in the NMR relaxation dispersion experiment occur and couple to isomerization reactions in molecular detail. In particular, we analyze the angular correlation functions of the backbone N–H bonds and find that slow conformational transitions occur at about the 3_10 helix in the apo state. These events at the helical region further affect the residues at about the ligand binding site. Unfolding of this helix leads to a tight hydrogen bond between the helical region and the ligand binding loop, thus forming a stable coiled structure. The helical and coiled structures are found to be characteristic of the Pin1–ligand complex with the ligand in the trans and cis states, respectively. These results indicate that the changes in the slow dynamics of Pin1 by the isomerization reaction occur via the shift in populations of the helical and coiled states, where the balance is dependent on the ligand isomerization states.

Molecular Insights into the Intrinsic Dynamics and Their Roles During Catalysis in Pin1 Peptidyl-prolyl Isomerase

Search this article

Description

Journal

Related Projects

Details 詳細情報について

Export

Report a problem