The human pathogen Clostridium difficile infection(CDI) is one of the most important healthcare- associated infections. Methyltransferase(MeTrca) and corrinoid iron-sulfur protein(CoFeSPca) are two key proteins ...The human pathogen Clostridium difficile infection(CDI) is one of the most important healthcare- associated infections. Methyltransferase(MeTrca) and corrinoid iron-sulfur protein(CoFeSPca) are two key proteins in the acetyl-coenzyme A synthesis pathway of Clostridium difficile, which is essential for the survival of the pathogen and is absent in humans. Hence, the interaction between MeTrca and CoFeSPcd can become innovative targets for the treatment of human CDI. In this study, the interaction between MeTrca and CoFeSPca was verified by fluorescence resonance energy transfer measurements. The influence of the interaction on the tertiary structure of MeTrcd and CoFeSPcd was studied by ANS-labeled fluorescence measurements. Molecular docking was also performed to understand the mechanism of the protein interactions. These results provide a molecular basis for innovative drug design and development to treat human CDI.展开更多
基金Supported by the National Natural Science Foundation of China(Nos.31270869, 31670817, 21472027, 91013001) and the Phl) Program of the Ministry of Education of China(No.20100071110011).
文摘The human pathogen Clostridium difficile infection(CDI) is one of the most important healthcare- associated infections. Methyltransferase(MeTrca) and corrinoid iron-sulfur protein(CoFeSPca) are two key proteins in the acetyl-coenzyme A synthesis pathway of Clostridium difficile, which is essential for the survival of the pathogen and is absent in humans. Hence, the interaction between MeTrca and CoFeSPcd can become innovative targets for the treatment of human CDI. In this study, the interaction between MeTrca and CoFeSPca was verified by fluorescence resonance energy transfer measurements. The influence of the interaction on the tertiary structure of MeTrcd and CoFeSPcd was studied by ANS-labeled fluorescence measurements. Molecular docking was also performed to understand the mechanism of the protein interactions. These results provide a molecular basis for innovative drug design and development to treat human CDI.