Goettle, Martin and Dove, Stefan and Kees, Frieder and Schlossmann, Jens and Geduhn, Jens and Koenig, Burkhard and Shen, Yuequan and Tang, Wei-Jen and Kaever, Volkhard and Seifert, Roland (2010) Cytidylyl and Uridylyl Cyclase Activity of Bacillus anthracis Edema Factor and Bordetella pertussis CyaA. BIOCHEMISTRY, 49 (26). pp. 5494-5503. ISSN 0006-2960,
Full text not available from this repository. (Request a copy)Abstract
Cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) are second messengers for numerous mammalian cell functions. The natural occurrence and synthesis of a third cyclic nucleotide (cNMP), cyclic cytidine 3',5'-monophosphate (cCMP), is a matter of controversy, and almost nothing is known about, cyclic uridine 3',5'-monophosphate (cUMP). Bacillus anthracis and Bordetella pertussis secrete the adenylyl cyclase (AC) toxins edema factor (EF) and CyaA, respectively, weakening immune responses and facilitating bacterial proliferation. A cell-permeable cCMP analogue inhibits human neutrophil superoxide production. Here, we report that EF and CyaA also possess cytidylyl cyclase (CC) and uridylyl cyclase (UC) activity. CC and UC activity was determined by a radiometric assay, using [alpha-P-32]CTP and [alpha-P-32]UTP as substrates, respectively, and by a high-performance liquid chromatography method. The identity of cNMPs was confirmed by mass spectrometry. On the basis of available crystal structures, we developed a model illustrating conversion of CTP to cCMP by bacterial toxins. In conclusion, we have shown both El: and CyaA have a rather broad substrate specificity and exhibit cytidylyl and uridylyl cyclase activity. Both cCMP and cUMP may contribute to toxin actions.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CYTIDINE 3'-5'-CYCLIC MONOPHOSPHATE; BOMBARDMENT MASS-SPECTROMETRY; MAMMALIAN ADENYLYL-CYCLASE; SOLUBLE GUANYLYL CYCLASE; STRUCTURAL BASIS; CYCLIC CMP; DIFFERENTIAL INHIBITION; PYRIMIDINE NUCLEOTIDES; RAT-TISSUES; CALMODULIN; |
| Subjects: | 600 Technology > 615 Pharmacy 600 Technology > 660 Chemical engineering |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Prof. Frieder Kees Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jul 2020 14:47 |
| Last Modified: | 22 Jul 2020 14:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24467 |
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