Mycobacterium tuberculosis sulfurtransferase SseA is activated by its neighboring gene product Rv3284

Tuberculosis remains a critical global health challenge, which underscores the need for new therapeutic targets. A potential drug target is the rhodanese-like thiosulfate sulfurtransferase SseA, which plays a role in macrophage infection by Mycobacterium tuberculosis (Mtb) and its resistance to oxidative stress. In our research, we identified a protein (Rv3284), herein referred to as SufE_Mtb, that interacts with SseA and modulates its activity. Sequence analysis and molecular modeling revealed that SufE_Mtb enhances SseA enzymatic function by binding to its non-catalytic N-terminal domain and favoring an activating conformational change in a regulatory loop of SseA. This interaction appears crucial for effective enzyme activity and the maintenance of redox homeostasis in Mtb, making the SseA-SufE_Mtb complex a potential target for new therapies.