Role of an orphan substrate-binding protein MhuP in transient heme transfer in Mycobacterium tuberculosis

The redox property of iron makes it an essential cofactor for numerous enzymes involved in various metabolic processes. In vertebrates, iron is attached to either heme molecules or with other circulatory proteins, making its accessibility restricted for bacterial pathogens residing inside the host. Due to this importance, there is always an ongoing battle between the host system and pathogens, known as nutritional immunity. To capture the bound iron from the human hosts, intracellular pathogens like Mycobacterium tuberculosis secrete siderophore molecules which are ultimately uptaken by versatile transport machinery such as ATP-binding cassette (ABC) transporters. Earlier reports have suggested the presence of a heme uptake protein MhuP (ORF id: Rv0265c) in M. tuberculosis, which transiently transfers the bound iron to the protein DppA for further heme transport by utilizing its cognate transport machinery (DppBCD). In the present study, we report the crystal structure of MhuP. The binding experiments of heme with MhuP suggest its specific nature. Molecular docking studies confirm the binding of the protein MhuP with heme as well as to the protein DppA. Thus, the results indicate the binding of heme to MhuP and its probable transient transport via the DppABCD transport system in M. tuberculosis.