Phosphodiesterase function and regulation

Covalent Binding of Boronic Acid-Based Inhibitor GSK4394835A to Phosphodiesterase 3B, a Drug Target for Cardiovascular Disease

The paper re-analyzes the crystal structure of PDE3B bound to GSK4394835A, revealing it as a reversible covalent inhibitor through boronate anion formation.

Divergent viral phosphodiesterases for immune signaling evasion

This study identifies diverse 2H phosphodiesterases in viruses that selectively degrade cyclic dinucleotides to evade host immune signaling.

Age-related increases in PDE11A4 protein expression trigger liquid:liquid phase separation (LLPS) of the enzyme that can be reversed by PDE11A4 small molecules inhibitors

This study shows that age-related PDE11A4 protein clustering in the hippocampus is due to liquid:liquid phase separation, which can be reversed by PDE11A inhibitors in vitro and in vivo.

Phosphodiesterase 3 inhibitors boost bone outgrowth

This study shows that PDE3 inhibitors enhance bone growth by increasing Ca2+ influx through TRPM7 channels in chondrocytes, suggesting potential repositioning for short stature syndromes.

Coevolving Residues Distant from the Ligand Binding Site are Involved in GAF Domain Function

The paper identifies two coevolving residues distant from the ligand binding site in GAF domains that are critical for allostery, using computational and experimental methods.

Phosphatases control the duration and range of cAMP/PKA microdomains

This study shows phosphatases control the duration and spatial range of cAMP/PKA microdomains by limiting phosphorylated PKA target activity.

Cross-pathway integration of cAMP signals through cGMP and calcium-regulated phosphodiesterases in mouse striatal cholinergic interneurons.

The paper investigates cAMP signaling dynamics in mouse striatal cholinergic interneurons, revealing distinct regulatory mechanisms involving phosphodiesterases and neuromodulators like NO and glutamate.

Amelioration of Functional and Histopathological Consequences after Spinal Cord Injury through Phosphodiesterase 4D (PDE4D) Inhibition

This study evaluates the effects of PDE4D inhibition on spinal cord injury outcomes, showing improved functional and histopathological results compared to PDE4B inhibition.

The sleep quality- and myopia-linked PDE11A-Y727C variant impacts neural physiology by reducing catalytic activity and altering subcellular compartmentalization of the enzyme

This paper investigates the impact of the PDE11A-Y727C variant on neural physiology, showing reduced catalytic activity and altered subcellular compartmentalization without significant effects on eye growth or sleep quality.

Unexpected proteinopathies in hippocampal PDE11A4 promote age-related cognitive decline of social associative memories

This study identifies age-related PDE11A4 proteinopathies in the hippocampus as contributors to cognitive decline in social associative memories.

Pivotal role of PDE10A in the integration of dopamine signals in mice striatal D1 and D2 medium-sized spiny neurones.

The paper investigates the role of PDE10A in dopamine signal integration in striatal D1 and D2 MSNs using FRET biosensors, finding that PDE10A uniquely reduces cAMP to baseline in both neuron types.

Investigating the role of N-terminal domain in phosphodiesterase 4B-inhibition by molecular dynamics simulation

This study uses molecular dynamics simulations to analyze the role of the N-terminal domain in PDE4B inhibitor binding and shows it enhances ligand affinity and stability.