Tan Xiangshi

Structural basis and molecular mechanism of soluble guanylate cyclase in NO-signaling transduction

Soluble guanylatecyclase (sGC), as a NO receptor, is a key metalloenzyme in mediating NO-signaling transduction. sGC is activated by NO to catalyze the conversion of guanosine 5-triphosphate (GTP) to cyclic guanylate monophosphate (cGMP). The dysfunction of NO signaling results in many pathological disorders, including several cardiovascular diseases such as arterial hypertension, pulmonary hypertension, heart failure and so on. Significant advances in its structure, function, mechanism, and physiological & pathological roles have been made throughout the past fifteen years. We herein review the progress of sGC on structural, functional investigations, as well as the proposed activation/deactivationmechanism. The heme-dependent sGC stimulators and heme-independent sGC activators have also been summarized briefly.

Insights into the Interactions Between Corrinoid Iron-sulfur Protein and Methyl Transferase from Human Pathogen Clostridium difficile

The human pathogen Clostridium difficile infection(CDI) is one of the most important healthcare-associated infections. Methyltransferase(MeTrCd) and corrinoid iron-sulfur protein(CoFeSPCd) 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 MeTrCd and CoFeSPCd can become innovative targets for the treatment of human CDI. In this study, the interaction between MeTrCd and CoFeSPCd 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.