Poster presentation
Crystal Structures of the Carboxyl cGMP Binding Domain of Plasmodium falciparum cGMP-Dependent Protein Kinase Reveals a Novel Salt Bridge Crucial for Activation
07/2013
Event name: 6th International Conference on cGMP
Description
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. However the development of a pfPKG-specific inhibitor has been greatly hampered by the lack of high-resolution structural information to guide rational drug design. Targeting the ATP binding site of pfPKG is an approach commonly associated with low specificity and toxicity. Therefore, we aim to target a domain that is unique to this kinase, the cyclic nucleotide binding (CNB) domain, to develop the antimalaria drug. Since previous studies demonstrated the fourth-cyclic nucleotide binding (CNB-D) domain of pfPKG to be the most important for the kinase activation, we focused on this domain to understand its role in cGMP dependent activation.
