Insights into the interactions between corrinoid iron-sulfur protein and methyl transferase from human pathogen Clostridium difficile

Abstract

The human pathogen Clostridium difficile infection(CDI) is one of the most important healthcare-associated infections. Methyltransferase(MeTr_Cd) and corrinoid iron-sulfur protein(CoFeSP_Cd) 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 MeTr_Cd and CoFeSP_Cd can become innovative targets for the treatment of human CDI. In this study, the interaction between MeTr_Cd and CoFeSP_Cd was verified by fluorescence resonance energy transfer measurements. The influence of the interaction on the tertiary structure of MeTr_Cd and CoFeSP_Cd 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.

Keywords

Corrinoid iron-sulfur protein / Methyl transferase / Clostridium difficile / Protein interaction

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