Thermodynamic and NMR Assessment of Ligand Cooperativity and Intersubunit Communication in Symmetric Dimers: Application to Thymidylate Synthase.

ABSTRACT: Thymidylate synthase (TS) is a homodimeric enzyme with evidence for negative regulation of one protomer while the other protomer acts on substrate, so called half-the-sites reactivity. The mechanisms by which multisubunit allosteric proteins communicate between protomers is not well understood, and the simplicity of dimeric systems has advantages for observing conformational and dynamic processes that functionally connect distance-separated active sites. This review considers progress in overcoming the inherent challenges of accurate thermodynamic and atomic-resolution characterization of interprotomer communication mechanisms in symmetric protein dimers, with TS used as an example. Isothermal titration calorimetry (ITC) is used to measure ligand binding cooperativity, even in cases where

SUBMITTER: Lee AL 

PROVIDER: S-EPMC5981203 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature