PMID:24074367

Citation	Goble, AM, Feng, Y, Raushel, FM and Cronan, JE (2013) Discovery of a cAMP deaminase that quenches cyclic AMP-dependent regulation. ACS Chem. Biol. 8:2622-9
Abstract	An enzyme of unknown function within the amidohydrolase superfamily was discovered to catalyze the hydrolysis of the universal second messenger, cyclic-3',5'-adenosine monophosphate (cAMP). The enzyme, which we have named CadD, is encoded by the human pathogenic bacterium Leptospira interrogans. Although CadD is annotated as an adenosine deaminase, the protein specifically deaminates cAMP to cyclic-3',5'-inosine monophosphate (cIMP) with a kcat/Km of 2.7 ± 0.4 × 10(5) M(-1) s(-1) and has no activity on adenosine, adenine, or 5'-adenosine monophosphate (AMP). This is the first identification of a deaminase specific for cAMP. Expression of CadD in Escherichia coli mimics the loss of adenylate cyclase in that it blocks growth on carbon sources that require the cAMP-CRP transcriptional activator complex for expression of the cognate genes. The cIMP reaction product cannot replace cAMP as the ligand for CRP binding to DNA in vitro and cIMP is a very poor competitor of cAMP activation of CRP for DNA binding. Transcriptional analyses indicate that CadD expression represses expression of several cAMP-CRP dependent genes. CadD adds a new activity to the cAMP metabolic network and may be a useful tool in intracellular study of cAMP-dependent processes.
Links	PubMed PMC3880142 Online version:10.1021/cb4004628
Keywords	Adenine; Adenosine; Adenosine Monophosphate; Adenylate Cyclase/genetics; Adenylate Cyclase/metabolism; Amino Acid Sequence; Bacterial Proteins/chemistry; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Cyclic AMP/metabolism; Cyclic AMP Receptor Protein/genetics; Cyclic AMP Receptor Protein/metabolism; Cyclic IMP/metabolism; DNA, Bacterial/metabolism; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Gene Expression Regulation, Bacterial; Kinetics; Leptospira interrogans/enzymology; Leptospira interrogans/genetics; Molecular Sequence Data; Nucleotide Deaminases/genetics; Nucleotide Deaminases/metabolism; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Substrate Specificity; Transcription, Genetic
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
LEPIC:Q72V44	enables	GO:0090612: cAMP deaminase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
LEPIC:Q72V44		GO:0090612: cAMP deaminase activity	ECO:0000314:		F		Figure 2, Panels E shows kinetic experiments to determine the in vitro activity. The first paragraph of the results and discussion provides the actual values for kcat/Km. Note has been corrected. This GO term was newly requested and created to make this annotation.	complete CACAO 10165

References

See Help:References for how to manage references in GONUTS.