Disorder and partial folding in the regulatory subunit hinge region of Trypanosoma brucei protein kinase A: The C-linker portion inhibits the parasite's protein kinase A

Abstract Microbial pathogens, such as Trypanosoma brucei, have an enormous impact on global health and economic systems. Protein kinase A of T. brucei is attractive drug target it essential enzyme which differs significantly from its human homolog. The hinge region this protein's regulatory domain vital for enzymatic function, but conformation unknown. Here, the secondary structure has been characterized using NMR CD spectroscopies. More specifically, three overlapping peptides corresponding to residues T187-I211, G198-Y223 V220–S245 called peptide 1, 2 3, respectively, were studied. 1 are chiefly unfolded; only low populations (