Emmanuel P. Bessay

TL;DR: CGMP addition increased binding affinity of [(3)H]tadalafil or [(3]H]vardenafil, implying that either inhibitor potentiates its own binding to PDE5 in intact cells by elevating cGMP.

TL;DR: Detailed characterized quaternary structures and cGMP-binding properties of 10 human PDE5A1 constructs containing one or both GAFs yield new insights into PDE4 functions, define boundaries that provide for allosteric cG MP binding, and identify regions that contribute to dimerization.

TL;DR: Conformational change(s) elicited by phosphorylation of the R domain within the PDE5 holoenzyme may also cause or participate in stimulating catalysis, and Migration in native polyacrylamide gels suggests that either cGMP binding orosphorylation produces distinct conformers of theR domain.

TL;DR: The combined results demonstrate that a conserved serine juxtaposed to the pseudosubstrate site in type I PKGs contributes importantly to enzyme function by increasing autoinhibition and decreasing cGMP binding affinity.

TL;DR: This work has provided the first evidence that PDE5 R domain, and GAF-B in particular, influences affinity and selectivity of the catalytic site for certain classes of inhibitors.