D. Kojetin

A tethering mechanism underlies Pin1-catalyzed proline cis-trans isomerization at a noncanonical site

This paper identifies a tethering mechanism by which Pin1 catalyzes proline cis-trans isomerization at a noncanonical site in the PPARγ AF-1 domain.

Unanticipated mechanisms of covalent inhibitor and synthetic ligand cobinding to PPARgamma

This study reveals that covalent PPARgamma inhibitors like GW9662 and T0070907 weaken but do not block binding of other synthetic ligands through an allosteric mechanism, altering the receptor's conformation and ligand binding affinity.

Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states

This study identifies a PPARγ ligand series that shifts the receptor's conformational ensemble between active and repressive states, revealing how subtle chemical changes influence its function.

Molecular basis of ligand-dependent Nurr1-RXRα activation

This study identifies a novel mechanism by which RXR ligands activate Nurr1-RXR transcriptional activity through disruption of the heterodimer interface.

Structural basis of interdomain communication in PPARγ

This study identifies a conserved Trp-Pro motif in PPARγ AF-1 that undergoes cis/trans isomerization, enabling interdomain communication with the LBD and affecting transcriptional activity.

Structural Mechanism Underlying Ligand Binding and Activation of PPARγ

This study reveals that PPARγ ligand binding involves a two-step induced fit mechanism, supported by NMR, SPR, and ITC analyses, with ligand entry through a surface pore and conformational changes leading to active helix 12 exposure.

Chemical Systems Biology Reveals Mechanisms of Glucocorticoid Receptor Signaling

The paper uses Ligand Class Analysis to identify target genes and coregulator interactions of glucocorticoid receptor ligands, revealing mechanisms linking ligand structure to physiological outcomes.

Assessment of NR4A Ligands that Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1

The paper assesses twelve NR4A ligands to determine if they directly bind and modulate Nurr1 or act through effector proteins, finding some bind directly while others do not.

Quantitative Structural Assessment of Graded Receptor Agonism

The paper quantifies how agonist structure affects PPARγ conformational changes, showing efficacy correlates with shifts toward active states detected by NMR.

Structural basis of altered potency and efficacy displayed by a major in vivo metabolite of the anti-diabetic PPARγ drug pioglitazone

This study compares the structure and function of pioglitazone and its metabolite 1-hydroxypioglitazone bound to PPARγ, showing reduced potency and efficacy of the metabolite.

A structural mechanism for directing inverse agonism of PPARγ

The paper shows how a phenyl-to-pyridyl substitution in PPARγ ligands converts an antagonist to an inverse agonist through a water-mediated hydrogen bond network involving Arg288.