Once acquired and shuttled into the bacterial cytoplasm, heme can be either directly incorporated into bacterial proteins or degraded by heme oxygenases. Pathogenic bacteria have evolved mechanisms that allow them to scavenge iron from the host, with several of these strategies targeted toward the uptake of heme. MhuD has not evolved to preferentially occupy the monoheme form and, through formation of a diheme complex, it functions as part of a larger network to tightly regulate both heme and iron levels in Mtb. Apomyoglobin heme transfer assays showed MhuD-diheme dissociation is far slower than monoheme dissociation at ∼0.12 min –1 and ∼0.25 s –1, respectively, indicating that MhuD has a strong affinity for diheme. Hence, diheme-MhuD is formed even when a large proportion of the MhuD population is in the apo form.
Native-mass spectrometry revealed little difference in binding affinity between solvent-exposed and solvent-protected hemes. Binding a second heme renders MhuD inactive, allowing heme storage.
#MASSLYNX SOFTWARE FREE#
Binding the first solvent-exposed heme allows heme degradation and releases free iron. The MhuD dimer binds up to two hemes within the active site of each monomer. The Mycobacterium tuberculosis ( Mtb) heme oxygenase MhuD liberates free iron by degrading heme to the linear tetrapyrrole mycobilin.
0 kommentar(er)
