Difference between revisions of "Part:BBa K1045003"
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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. | 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 | + | 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> | <p> | ||
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| + | [[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)]] | ||
<html> | <html> | ||
| − | < | + | <object width="420" height="315"><param name="movie" value="//www.youtube.com/v/T0xpaOZtjfk?hl=zh_CN&version=3&rel=0"></param> |
| − | width="420" height=" | + | <param name="allowFullScreen" value="true"></param> |
| − | src=" | + | <param name="allowscriptaccess" value="always"></param> |
| − | type="application/x-shockwave-flash"> | + | <embed src="//www.youtube.com/v/T0xpaOZtjfk?hl=zh_CN&version=3&rel=0" type="application/x-shockwave-flash" width="420" height="315" allowscriptaccess="always" allowfullscreen="true"> |
| − | </embed></html> | + | </embed></object></html> |
| − | </p> | + | </br> </p> |
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| + | 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 | <!-- Add more about the biology of this part here | ||
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.
</br>
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
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]