Enzymes use transition metals as co-factors for catalytic roles in biological processes. Notably, manganese, iron, cobalt, nickel, copper and zinc are abundantly used. Staphylococcus aureus, a commensal bacterium asymptomatically, lies on the human body causing variety of infections. S. aureus is equipped by advanced virulence-regulatory circuits of metal acquisition like Cnt that acquires metals at infection sites by utilizing a nicotianamine-like metallophore staphylopine. Despite significant growth in structural studies, how CntA of Cnt system transmits conformational signal upon staphylopine recognition remains elusive. Here, we analyzed the structural changes adopted by CntA during close-to-open transition by computational approaches. CntA uses a bi-domain architectural form of domain II which performed 37° rigid body rotation and 1.1 Å translation assisted by inter-domain hinge cluster residues. Important clustered communities were found regulating the conformational changes in CntA where communities 4 and 5 are found crucial. Besides open and close states, the fluctuating regions sampled two additional intermediate states which were considered close or open previously. CntA prefers fluctuating the non-conserved regions rather than conserved where domain II turned out to be rigid and maintains a stable fold. Overall, the CntA system is a potential target for structural biologist to hamper such conformational behaviors at family level.Communicated by Ramaswamy H. Sarma.
Keywords: Metal importers; elastic network model; nickle binding; protein conformational changes; staphylopine.