Eugen Franz

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A-kinase anchoring proteins (AKAPs) play an important role in the spatial and temporal regulation of protein kinase A (PKA) by scaffolding critical intracellular signaling complexes. Here we report the design of conformationally constrained peptides that disrupt interactions between PKA and AKAPs in an isoform-selective manner. Peptides derived from the A(More)
A-Kinase Anchoring Proteins (AKAPs) coordinate complex signaling events by serving as spatiotemporal modulators of cAMP-dependent protein kinase activity in cells. Although AKAPs organize a plethora of diverse pathways, their cellular roles are often elusive due to the dynamic nature of these signaling complexes. AKAPs can interact with the type I or type(More)
The Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) is a key regulator across the malaria parasite life cycle. Little is known about PfPKG's activation mechanism. Here we report that the carboxyl cyclic nucleotide binding domain functions as a "gatekeeper" for activation by providing the highest cGMP affinity and selectivity. To understand the(More)
Background cAMP-dependent protein kinase (PKA) and cGMPdependent protein kinase (PKG) are the main effectors of distinct cyclic nucleotide pathways and are preferentially activated by cAMP or cGMP, respectively. We recently characterized the isolated C-terminal cyclic nucleotide binding domain (CNB-B) of the human PKG Ib as highly cGMP-selective (manuscript(More)
This correction is in regard to Figure 3a. Compound 2K-3 contains a typo in its sequence at position 13 (S instead of K). The sequence should read KKLAKFLVS*ALK*ALK. Its scramble control, 2K-3-scramble, is listed correctly. Compound analysis and all experiments were performed using the compound with the correct sequence. This typo does not change any of the(More)
Background Plasmodium falciparum cGMP-dependent protein kinase (pfPKG) is a validated therapeutic target of malaria. As a key regulator of its life cycle, pfPKG plays a crucial role in both the sexual and asexual blood-stages that cause malaria pathology. Inhibiting pfPKG blocks proliferation and transmission of the parasite [1,2]. However the development(More)
s from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications Bamberg, Germany. 23-25 June, 2017 Published: 10 October 2017 A1 Characterization and development of next-generation sGC stimulators G. Todd Milne (tmilne@ironwoodpharma.com), on behalf of the Ironwood team Ironwood Pharmaceuticals, Cambridge, MA 02142, USA(More)
Background Malaria is one of the most dangerous tropical diseases worldwide, resulting in approximately 1.5-2.7 million deaths per year [1]. Furthermore, malaria belongs to the four major infectious diseases also including HIV, tuberculosis and hepatitis. In humans, malaria is transmitted by four species of the genus Plasmodium. However, most malaria deaths(More)
Cyclic GMP analogs, 8-Br, 8-pCPT, and PET-cGMP, have been widely used for characterizing cellular functions of cGMP-dependent protein kinase (PKG) I and II isotypes. However, interpreting results obtained using these analogs has been difficult due to their low isotype specificity. Additionally, each isotype has two binding sites with different cGMP(More)
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