Difference between revisions of "Part:BBa K1045003"

Latest revision as of 15:25, 29 September 2018

Diadenylate cyclase domain of Listeria monocytogenes cdaA (DacA)

The severe threat caused by bacteria which are resistant to conventional antibiotic drugs and the appearance of even multi-resistant strains demonstrates the urgent need for the discovery of new antibacterial substance classes. Cyclic di-AMP was discovered to be an essential signal molecule in Gram-positive bacteria including the pathogenic species Streptococcus pneumoniae, Staphylococcus aureus and Listeria monocytogenes. Both, loss and overproduction of c-di-AMP have detrimental effects on cell growth, cell wall synthesis, and propagation. Thus, the diadenylate cyclase (DAC) which catalyses the condensation reaction of two ATP molecules to c-di-AMP is the key factor for signal molecule production and maintenance of c-di-AMP homeostasis. We are convinced that the DAC is a very promising target for the development of highly specific antibiotic substances which exclusively act on Gram-positive bacteria and are not harmful to Gram-negative ones, including the gut bacterium Escherichia coli as well as humans. Here, we introduce a truncated but functional DAC which localizes to the cytosol and can easily be purified.
Furthermore, the protein was crystallized and the X-ray diffraction pattern obtained. This enabled the determination of the 3D-structure of DacA by Molecular Replacement using the similar diadenylate cyclase DisA from B. subtilis.

Fig. 1. c-di-AMP production and degradation. c-di-AMP is produced from two molecules of ATP by DACs and degraded to pApA by phosphodiasterases. (Edited from Corrigan and Gründling, 2013)

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The part BBa_K1045003 described here, covers the amino acids 100 to 273 of the full length coding sequence of CdaA. For a precise description of this part, please vistit the experience page!

Sequence and Features

Assembly Compatibility:

10
COMPATIBLE WITH RFC[10]
12
COMPATIBLE WITH RFC[12]
21
COMPATIBLE WITH RFC[21]
23
COMPATIBLE WITH RFC[23]
25
COMPATIBLE WITH RFC[25]
1000
COMPATIBLE WITH RFC[1000]

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 The severe threat caused by bacteria which are resistant to conventional antibiotic drugs and the appearance of even multi-resistant strains demonstrates the urgent need for the discovery of new antibacterial substance classes.
-Cyclic di-AMP was discovered to be an essential signal molecule in Gram-positive bacteria including the pathogenic species ''Streptococcus pneumoniae'', ''Staphylococcus aureus'' and ''Listeria monocytogenes''. Both, loss and overproduction of c-di-AMP have detrimental effects on cell growth, cell wall synthesis, and propagation. Thus, the diadenylate cyclase (DAC) which catalyses the condensation reaction of two ATP molecules to c-di-AMP is the key factor for signal molecule production and maintenance of c-di-AMP homeostasis. We are convinced that the DAC is a very promising target for the development of highly specific antibiotic substances which exclusively act on Gram-positive bacteria and are not harmful to Gram-negative ones, including the gut bacterium ''Escherichia coli'' as well as humans. Here, we introduce a truncated but functional DAC which localizes to the cytosol and can easily be purified. Furthermore, protein crystals were obtained as well as the protein structure by X-ray diffraction analysis. The part [[Part:BBa_K1045003|BBa_K1045003]] described here, covers the amino acids 100 to 273 of the full length coding sequence of CdaA. <br /> For a precise description of this part, please vistit the experience page!
+Cyclic di-AMP was discovered to be an essential signal molecule in Gram-positive bacteria including the pathogenic species ''Streptococcus pneumoniae'', ''Staphylococcus aureus'' and ''Listeria monocytogenes''. Both, loss and overproduction of c-di-AMP have detrimental effects on cell growth, cell wall synthesis, and propagation. Thus, the diadenylate cyclase (DAC) which catalyses the condensation reaction of two ATP molecules to c-di-AMP is the key factor for signal molecule production and maintenance of c-di-AMP homeostasis. We are convinced that the DAC is a very promising target for the development of highly specific antibiotic substances which exclusively act on Gram-positive bacteria and are not harmful to Gram-negative ones, including the gut bacterium ''Escherichia coli'' as well as humans. Here, we introduce a truncated but functional DAC which localizes to the cytosol and can easily be purified. <br />
+Furthermore, the protein was crystallized and the X-ray diffraction pattern obtained. This enabled the determination of the 3D-structure of DacA by Molecular Replacement using the similar diadenylate cyclase DisA from ''B. subtilis''.
 <p>
-[[File:image002.png|400px|thumb|left|'''Fig. 1. c-di-AMP production and degradation.''' c-di-AMP is produced from two molecules of ATP by DACs and degraded to pApA by phosphodiasterases. (Edited from Corrigan and Gründling, 2013)]]
+[[File:image002.png|370px|thumb|left|'''Fig. 1. c-di-AMP production and degradation.''' c-di-AMP is produced from two molecules of ATP by DACs and degraded to pApA by phosphodiasterases. (Edited from Corrigan and Gründling, 2013)]]
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 <embed src="//www.youtube.com/v/T0xpaOZtjfk?hl=zh_CN&amp;version=3&amp;rel=0" type="application/x-shockwave-flash" width="420" height="315" allowscriptaccess="always" allowfullscreen="true">
 </embed></object></html>
-</p>
+</br> </p>
-<br />
+The part [[Part:BBa_K1045003|BBa_K1045003]] described here, covers the amino acids 100 to 273 of the full length coding sequence of CdaA. For a precise description of this part, please vistit the experience page! <br />
 <!-- Add more about the biology of this part here