Bacillus anthracis Edema Factor Substrate Specificity: Evidence for New Modes of Action
Abstract
:Abbreviations:
AC | adenylyl cyclase |
ACD | adenylyl cyclase domain |
ANT | anthraniloyl |
EF | edema factor AC toxin from Bacillus anthracis |
CaM | calmodulin |
cAMP | cyclic adenosine 3′:5′-monophosphate |
ANTXR | anthrax toxin receptor |
CC | cytidylyl cyclase |
cCMP | cyclic cytidine 3′:5′-monophosphate |
cIMP | cyclic inosine 3′:5′-monophosphate |
CMG2 | capillary morphogenesis gene 2 |
cNMP | cyclic nucleoside 3′:5′-monophosphate |
CREB | cAMP response element-binding |
cUMP | cyclic uridine 3′:5′-monophosphate |
cXMP | cyclic xanthosine 3′:5′-monophosphate |
IBMX | 3-isobutyl-1-methylxanthine |
IC | inosylyl cyclase |
LF | lethal factor |
mAC | membranous mammalian AC |
MAPK | mitogen-activated protein kinase |
MAPKK | mitogen-activated protein kinase kinase |
MANT | methylanthraniloyl |
MRP | multidrug resistance protein |
MS | mass spectrometry |
NTP | nucleoside 5′-triphosphate |
PA | protective antigen |
PDE | phosphodiesterase |
PKA | cAMP-dependent protein kinase |
PKG | cGMP-dependent protein kinase |
PMEApp | 9-[2-(phosphonomethoxy)ethyl]adenine diphosphate |
PMN | polymorphonuclear leukocytes |
sGC | soluble mammalian guanylyl cyclase |
TEM | transendothelial migration |
TEM8 | tumor endothelial marker 8 |
UC | uridylyl cyclase |
1. The cAMP Signaling Pathway
2. The Fatal Synergism of Bacillus anthracis Exotoxin Components
3. Substrate-Specificity of EF: cCMP, cUMP and cIMP as Potential New Second Messengers
Inhibitor | AC 1 (nM) | AC 2 (nM) | AC 5 (nM) | EF (nM) |
---|---|---|---|---|
MANT-ATP | 150 | 330 | 100 | 580 |
MANT-ITP | 2.8 | 14 | 1.2 | 4,100 |
MANT-GTP | 90 | 620 | 55 | 2,500 |
MANT-CTP | 150 | 690 | 150 | 100 |
MANT-UTP | 46 | 460 | 32 | 3,700 |
Enzyme | NC activity | Me2+ | Km [µM] | kcat [s-1] |
---|---|---|---|---|
EF | AC | Mn2+ | 35.3 ± 3.7 | 501.5 ± 55.9 |
Mg2+ | 175.8 ± 29.9 | 684.2 ± 272.5 | ||
CC | Mn2+ | 12.5 ± 3.4 | 8.8 ± 1.4 | |
Mg2+ | 419.7 ± 115.1 | 7.2 ± 3.1 | ||
UC | Mn2+ | 134.5 ± 23.5 | 2.3 ± 0.2 |
4. EF Structure and Nucleotide Binding Modes
5. Potential Cellular Targets of Novel Cyclic Nucleotides: Protein Kinases, Phosphodiesterases and Cyclic Nucleotide-Gated Ion Channels
5.1. Protein Kinases (PKs)
5.2. Cyclic Nucleotide Phosphodiesterases (PDEs)
5.3. Cyclic Nucleotide-Gated Ion Channels (CNGs)
6. Unresolved Questions and Future Studies
7. Conclusions
Acknowledgements
Conflict of Interest
References
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Göttle, M.; Dove, S.; Seifert, R. Bacillus anthracis Edema Factor Substrate Specificity: Evidence for New Modes of Action. Toxins 2012, 4, 505-535. https://doi.org/10.3390/toxins4070505
Göttle M, Dove S, Seifert R. Bacillus anthracis Edema Factor Substrate Specificity: Evidence for New Modes of Action. Toxins. 2012; 4(7):505-535. https://doi.org/10.3390/toxins4070505
Chicago/Turabian StyleGöttle, Martin, Stefan Dove, and Roland Seifert. 2012. "Bacillus anthracis Edema Factor Substrate Specificity: Evidence for New Modes of Action" Toxins 4, no. 7: 505-535. https://doi.org/10.3390/toxins4070505