Phosphorylation of mycobacterial phosphodiesterase by eukaryotic-type Ser/Thr kinase controls its two distinct and mutually exclusive functionalities.

ABSTRACT: Phosphorylation-mediated negative feedback regulation of cAMP levels by phosphodiesterase is well-established in eukaryotic cells. However, such a mechanism remains unexplored in prokaryotes. We report here the involvement of eukaryotic-type Ser/Thr kinases, particularly PknA in trans-phosphorylating phosphodiesterase from Mycobacterium tuberculosis (mPDE), that resulted in decreased enzyme turnover rate compared with its unphosphorylated counterpart. To elucidate the role of mPDE phosphorylation in hydrolyzing cellular cAMP, we utilized a phosphodiesterase knock-out Escherichia coli strain, ΔcpdA, where interference of endogenous eukaryotic-type Ser/Thr kinases could be excluded. Interestingly, the mPDE-complemented ΔcpdA strain showed enhanced cAMP levels in t

SUBMITTER: Malhotra N 

PROVIDER: S-EPMC5655513 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature