Nanosecond-Timescale Dynamics and Conformational Heterogeneity in Human GCK Regulation and Disease.

ABSTRACT: Human glucokinase (GCK) is the prototypic example of an emerging class of proteins with allosteric-like behavior that originates from intrinsic polypeptide dynamics. High-resolution NMR investigations of GCK have elucidated millisecond-timescale dynamics underlying allostery. In contrast, faster motions have remained underexplored, hindering the development of a comprehensive model of cooperativity. Here, we map nanosecond-timescale dynamics and structural heterogeneity in GCK using a combination of unnatural amino acid incorporation, time-resolved fluorescence, and ¹⁹F nuclear magnetic resonance spectroscopy. We find that a probe inserted within the enzyme's intrinsically disordered loop samples multiple conformations in the unliganded state. Glucose binding and disease-associa

SUBMITTER: Sternisha SM 

PROVIDER: S-EPMC7063420 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature