Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A genetic selection procedure has been developed which makes the growth of E. coli dependent on expression of a cGMP phosphodiesterase cDNA. E. coli does not contain a cGMP phosphodiesterase, and guanine auxotrophs cannot extract the guanine from cGMP. If a functional cGMP phosphodiesterase is introduced, then guaA auxotrophs will grow on cGMP as a guanine source. The method also selects GMP synthetase cDNAs, which complement the guanine auxotrophy directly. Expression of a Dictyostelium discoideum or human heart cyclic nucleotide phosphodiesterase cDNA permits growth of the E. coli guaA auxotroph in the presence of cGMP. Several commercial cDNA libraries were corrupt and contained phosphodiesterase and/or GMP synthetase sequences that were from a contaminating DNA source.
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PMID:Selection of cDNAs for phosphodiesterases that hydrolyze guanosine 3';5'-monophosphate in Escherichia coli. 134 38

While studying virulence gene regulation in Vibrio cholerae during infection of the host small intestine, we identified VieA as a two-component response regulator that contributes to activating expression of cholera toxin. Here we report that VieA represses transcription of Vibrio exopolysaccharide synthesis (vps) genes involved in biofilm formation by a mechanism independent of its phosphorelay and DNA-binding activities. VieA controls the intracellular concentration of the cyclic nucleotide second messenger cyclic diguanylate (c-di-GMP) using an EAL domain that functions as a c-di-GMP phosphodiesterase. Two-dimensional thin layer chromatography of nucleotide extracts confirmed that VieA reduces the concentration of c-di-GMP, opposing the action of c-di-GMP synthetase proteins. Expression of unrelated V. cholerae c-di-GMP synthetase or phosphodiesterae proteins also modulated c-di-GMP concentration and vps gene expression. We propose that c-di-GMP synthetase and phosphodiesterase domain-containing proteins contribute to regulating biofilm formation by controlling c-di-GMP concentration.
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PMID:Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation. 1525 98

The universal and pleiotropic cyclic dinucleotide second messenger c-di-GMP is most prominently known to inversely regulate planktonic and sessile lifestyles of Gram-negative species. In the Gram-positive model organism Bacillus subtilis, intracellular c-di-GMP levels are modulated by a concise set of three diguanylate cylases (DgcK, DgcP, DgcW) and one phosphodiesterase (PdeH). Two recent studies have reported the negative influence of the c-di-GMP receptor DgrA (PilZ domain protein) on swarming motility indicating a conserved role of this second messenger across the bacterial domain. However, it has been suggested that the degenerated GGDEF protein YdaK and the inactive EAL domain protein YkuI may also function as c-di-GMP receptors regulating potentially other processes than motility. Here we describe a novel c-di-GMP dependent signaling network in B. subtilis regulating the production of an unknown exopolysaccharide (EPS) that leads to strongly altered colony morphologies upon overproduction. The network consists of the c-di-GMP receptor YdaK and the c-di-GMP synthetase DgcK. Both proteins establish a spatially close signal-effector cluster at the membrane. The cytoplasmic DgcP synthetase can complement for DgcK only upon overproduction, while the third c-di-GMP synthetase, DgcW, of B. subtilis is not part of the signaling pathway. Removal of the regulatory EAL domain from DgcW reveals a distinct function in biofilm formation. Therefore, our study is compatible with the "local pool signaling" hypothesis, but shows that in case of the yda operon, this can easily be overcome by overproduction of non-cognate DGCs, indicating that global pools can also confer signals to regulatory circuits in a Gram-positive bacterium.
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PMID:New Functions and Subcellular Localization Patterns of c-di-GMP Components (GGDEF Domain Proteins) in B. subtilis. 2853 59