Michael J. Chalmers

TL;DR: Findings strongly suggest that Cdk5-mediated phosphorylation of PPARγ may be involved in the pathogenesis of insulin-resistance, and present an opportunity for development of an improved generation of anti-diabetic drugs throughPPARγ.

TL;DR: Novel synthetic compounds are described that have a unique mode of binding to PPARγ, completely lack classical transcriptional agonism and block the Cdk5-mediated phosphorylation in cultured adipocytes and in insulin-resistant mice, and one such compound, SR1664, has potent antidiabetic activity while not causing the fluid retention and weight gain that are serious side effects of many of the PParγ drugs.

TL;DR: Structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites.

TL;DR: The gradient of PPARgamma transactivation cannot be accounted for solely through changes to the dynamics of AF-2, so the understanding of allosteric signaling must be extended beyond the idea of a dynamic helix 12 acting as a molecular switch.

TL;DR: The utility of this system to differentiate structural perturbations in the ligand-binding domain (LBD) of the nuclear receptor PPARgamma induced upon binding a full agonist and a partial agonist is demonstrated.