PMID:15882424

Citation	Rajagopal, L, Vo, A, Silvestroni, A and Rubens, CE (2005) Regulation of purine biosynthesis by a eukaryotic-type kinase in Streptococcus agalactiae. Mol. Microbiol. 56:1329-46
Abstract	Group B streptococci (GBS) are the principal causal agents of human neonatal pneumonia, sepsis and meningitis. We had previously described the existence of a eukaryotic-type serine/threonine kinase (Stk1) and phosphatase (Stp1) in GBS that regulate growth and virulence of the pathogen. Our previous results also demonstrated that these enzymes reversibly phosphorylated an inorganic pyrophosphatase. To understand the role of these eukaryotic-type enzymes on growth of GBS, we assessed the stk1-mutants for auxotrophic requirements. In this report, we describe that in the absence of the kinase (Stk1), GBS are attenuated for de novo purine biosynthesis and are consequently growth arrested. During growth in media lacking purines, the intracellular G nucleotide pools (GTP, GDP and GMP) are significantly reduced in the Stk1-deficient strains, while levels of A nucleotides (ATP, ADP and AMP) are marginally increased when compared with the isogenic wild-type strain. We provide evidence that the reduced pools of G nucleotides result from altered activity of the IMP utilizing enzymes, adenylosuccinate synthetase (PurA) and IMP dehydrogenase (GuaB) in these strains. We also demonstrate that Stk1 and Stp1 reversibly phosphorylate and consequently regulate PurA activity in GBS. Collectively, these data indicate the novel role of eukaryotic-type kinases in regulation of metabolic processes such as purine biosynthesis.
Links	PubMed PMC2366208 Online version:10.1111/j.1365-2958.2005.04620.x
Keywords	5'-Guanylic Acid/analysis; Adenosine Diphosphate/metabolism; Adenosine Monophosphate/metabolism; Adenosine Triphosphate/metabolism; Adenylosuccinate Synthase/metabolism; Genetic Complementation Test; Guanosine Diphosphate/metabolism; Guanosine Triphosphate/metabolism; IMP Dehydrogenase/metabolism; Mutation; Phosphorylation; Phosphotransferases/genetics; Phosphotransferases/metabolism; Purines/biosynthesis; Streptococcus agalactiae/genetics; Streptococcus agalactiae/growth & development; Streptococcus agalactiae/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
STRA1:PURA		GO:0004019: adenylosuccinate synthase activity	ECO:0000314:		F		Table 5	complete CACAO 5519
STRA1:PURA	enables	GO:0004019: adenylosuccinate synthase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
STRAG:Q8VQA0		GO:0006470: protein dephosphorylation	ECO:0000314:		P		Figure 6, Lane 1	complete CACAO 5502
STRAG:Q8VQA0		GO:0004721: phosphoprotein phosphatase activity	ECO:0000314:		F		Figure 6	complete CACAO 5503
STRAG:Q8VQA0		GO:0006468: protein phosphorylation	ECO:0000314:		P		Figure 6	complete CACAO 5500

References

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