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Nishinaga et al. present structural characterization of the transcription regulator PefR from S. agalactiae in different states (apo-, DNAbound, heme-bound, CO-heme-bound and CN-heme-bound-PefRs). Structural comparison revealed that unique heme coordination controls structural rearrangement for the survival of the neonatal infection-causing hemolytic bacteria.

Corynebacteria contain a heme uptake system encoded in hmuTUV genes, in which HmuT protein acts as a heme binding protein to transport heme to the cognate transporter HmuUV. The crystal structure of HmuT from Corynebacterium glutamicum (CgHmuT) reveals that heme is accommodated in the central cleft with His141 and Tyr240 as the axial ligands and that Tyr240 forms a hydrogen bond with Arg242. In this work, the crystal structures of H141A, Y240A, and R242A mutants were determined to understand the role of these residues for the heme binding of CgHmuT. Overall and heme environmental structures of these mutants were similar to those of the wild type, suggesting that there is little conformational change in the heme-binding cleft during heme transport reaction with binding and the dissociation of heme. A loss of one axial ligand or the hydrogen bonding interaction with Tyr240 resulted in an increase in the redox potential of the heme for CgHmuT to be reduced by dithionite, though the wild type was not reduced under physiological conditions. These results suggest that the heme environmental structure stabilizes the ferric heme binding in CgHmuT, which will be responsible for efficient heme uptake under aerobic conditions where Corynebacteria grow. [ABSTRACT FROM AUTHOR]

Malaria parasites digest hemoglobin within a food vacuole to supply amino acids, releasing the toxic product heme. During the detoxification, toxic free heme is converted into an insoluble crystalline form called hemozoin (Hz). Heme detoxification protein (HDP) in Plasmodium falciparum is one of the most potent of the hemozoin-producing enzymes. However, the reaction mechanisms of HDP are poorly understood. We identified the active site residues in HDP using a combination of Hz formation assay and spectroscopic characterization of mutant proteins. Replacement of the critical histidine residues His122, His172, His175, and His197 resulted in a reduction in the Hz formation activity to approximately 50% of the wild-type protein. Spectroscopic characterization of histidine-substituted mutants revealed that His122 binds heme and that His172 and His175 form a part of another heme-binding site. Our results show that the histidine residues could be present in the individual active sites and could be ligated to each heme. The interaction between heme and the histidine residues would serve as a molecular tether, allowing the proper positioning of two hemes to enable heme dimer formation. The heme dimer would act as a seed for the crystal growth of Hz in P. falciparum. [ABSTRACT FROM AUTHOR]

Diatomic gas molecules such as O2, CO and NO act as signaling molecules in many biological systems, where metal-containing gas sensor proteins sense their effector gas molecules by using prosthetic groups such as heme, iron–sulfur clusters and non-heme iron as the active center for gas sensing. When the gas sensor proteins sense their effector gas molecules, intramolecular and intermolecular signal transductions take place to regulate many physiological functions including gene expression, aerotaxis, and change in metabolic pathways, etc. The metal-containing prosthetic groups in these sensor proteins play a crucial role for selective sensing of their effectors. In this perspective, I will discuss the structure and function of some O2-, CO- and NO-sensor proteins, especially focussing on the structural, biochemical and biophysical properties of the active centers of these sensor proteins. [ABSTRACT FROM AUTHOR]