Luebker, Carolin and Dove, Stefan and Tang, Wei-Jen and Urbauer, Ramona J. Bieber and Moskovitz, Jackob and Urbauer, Jeffrey L. and Seifert, Roland (2015) Different Roles of N-Terminal and C-Terminal Domains in Calmodulin for Activation of Bacillus anthracis Edema Factor. TOXINS, 7 (7). pp. 2598-2614. ISSN 2072-6651,
Full text not available from this repository. (Request a copy)Abstract
Bacillus anthracis adenylyl cyclase toxin edema factor (EF) is one component of the anthrax toxin and is essential for establishing anthrax disease. EF activation by the eukaryotic Ca2+-sensor calmodulin (CaM) leads to massive cAMP production resulting in edema. cAMP also inhibits the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, thus reducing production of reactive oxygen species (ROS) used for host defense in activated neutrophils and thereby facilitating bacterial growth. Methionine (Met) residues in CaM, important for interactions between CaM and its binding partners, can be oxidized by ROS. We investigated the impact of site-specific oxidation of Met in CaM on EF activation using thirteen CaM-mutants (CaM-mut) with Met to leucine (Leu) substitutions. EF activation shows high resistance to oxidative modifications in CaM. An intact structure in the C-terminal region of oxidized CaM is sufficient for major EF activation despite altered secondary structure in the N-terminal region associated with Met oxidation. The secondary structures of CaM-mut were determined and described in previous studies from our group. Thus, excess cAMP production and the associated impairment of host defence may be afforded even under oxidative conditions in activated neutrophils.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | METHIONINE SULFOXIDE REDUCTASE; ADENYLYL-CYCLASE TOXIN; OXIDIZED CALMODULIN; STRUCTURAL BASIS; OXIDATION; BINDING; REPAIR; RECOGNITION; BACTERIAL; MUTANTS; Bacillus anthracis edema factor; adenylyl cyclase toxin; (oxidized) calmodulin; (oxidized) calmodulin mutants |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Jul 2019 08:13 |
| Last Modified: | 08 Jul 2019 08:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5235 |
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