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1.
Mol Cell ; 82(24): 4712-4726.e7, 2022 12 15.
Article in English | MEDLINE | ID: mdl-36423631

ABSTRACT

Programmed cell death and caspase proteins play a pivotal role in host innate immune response combating pathogen infections. Blocking cell death is employed by many bacterial pathogens as a universal virulence strategy. CopC family type III effectors, including CopC from an environmental pathogen Chromobacterium violaceum, utilize calmodulin (CaM) as a co-factor to inactivate caspases by arginine ADPR deacylization. However, the molecular basis of the catalytic and substrate/co-factor binding mechanism is unknown. Here, we determine successive cryo-EM structures of CaM-CopC-caspase-3 ternary complex in pre-reaction, transition, and post-reaction states, which elucidate a multistep enzymatic mechanism of CopC-catalyzed ADPR deacylization. Moreover, we capture a snapshot of the detachment of modified caspase-3 from CopC. These structural insights are validated by mutagenesis analyses of CopC-mediated ADPR deacylization in vitro and animal infection in vivo. Our study offers a structural framework for understanding the molecular basis of arginine ADPR deacylization catalyzed by the CopC family.


Subject(s)
Calmodulin , Caspases , Animals , Calmodulin/genetics , Calmodulin/metabolism , Caspases/metabolism , Caspase 3/metabolism , Arginine , Catalysis , Bacterial Proteins/genetics , Bacterial Proteins/metabolism
2.
ACS Appl Mater Interfaces ; 10(35): 29467-29475, 2018 Sep 05.
Article in English | MEDLINE | ID: mdl-30091894

ABSTRACT

Microwave-induced catalytic degradation is considered amongst the most efficient techniques to remove antibiotic such as chlortetracycline from contaminated water. Described here is a new microwave-induced oxidation catalyst based on carbon nanotubes (CNTs) decorated uniformly with nanoparticles of Fe3O4. The combination of dielectric loss and magnetic loss of the material contributed to its stronger microwave absorption and the ability to produce more "hot spots". These hot spots promoted the oxidation of common antibiotics such as chlortetracycline, tetracycline, and oxytetracycline under microwave irradiation. Experiments with the addition of scavenger showed that hydroxy radicals (•OH) together with superoxide radicals (•O2-) contributed to the antibiotics removal as well. The final degradation products included CO2 and NO3- as confirmed by mass spectroscopy and ion chromatography analyses. The results indicated that the Fe3O4/CNTs was an efficient catalyst for microwave-induced oxidation.


Subject(s)
Anti-Bacterial Agents , Ferric Compounds/chemistry , Metal Nanoparticles/chemistry , Microwaves , Nanotubes, Carbon , Anti-Bacterial Agents/chemistry , Catalysis , Water Pollutants/chemistry , Water Purification
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