Disease relevance of HEME

• The attachment of the lysine-ligated heme group requires specialized proteins in W. succinogenes and Escherichia coli that are encoded by accessory nrf genes [1].
• Nitrous oxide reductase from Wolinella succinogenes, an enzyme containing one heme c and four Cu atoms/subunit of Mr = 88,000, was studied by electron paramagnetic resonance (EPR) at 9.2 GHz from 6 to 80 K [2].
• Six erythromycin-resistant campylobacter strains were investigated by 16S ribosomal DNA (rDNA) sequencing, 23S rDNA sequencing, and restriction fragment length polymorphism analysis of a putative heme-copper oxidase domain described as being specific for thermophilic Campylobacter species [3].

High impact information on HEME

• The active site heme c group of NrfA proteins from different bacteria is covalently bound via the cysteine residues of a unique CXXCK motif [1].
• The lysine residue of this motif serves as an axial ligand to the heme iron thus replacing the conventional histidine residue [1].
• The simulation offers insight into why Sdh4p Cys-78 may be serving as the second axial ligand for the heme instead of a histidine residue [4].
• The results indicate that both heme b groups are involved in electron transport and that the architecture of the menaquinone reduction site near the cytoplasmic side of the membrane is similar to that proposed for E. coli FdnI [5].
• The four histidine residues predicted as axial heme b ligands were individually replaced by alanine in Strep-tagged HydC [5].

Chemical compound and disease context of HEME

• The nature of the heme centers in the hexa-heme dissimilatory nitrite reductase from the bacterium Wolinella succinogenes has been investigated with EPR and magnetic circular dichroism spectroscopy [6].

Biological context of HEME

• We discuss the possible roles of heme and of the two quinone-binding sites in electron transport [4].
• Functionally important residues identified by mutagenesis of the SDH3 and SDH4 genes are located near the two proposed quinone-binding sites, which are separated by the heme [4].
• The quinol:fumarate reductase of Wolinella succinogenes binds a low- and a high-potential heme b group in its transmembrane subunit C. Both hemes are part of the electron transport chain between the two catalytic sites of this redox enzyme [7].
• Comparison of the encoded sequences with previously determined sequences suggests that these genes constitute part of a thiosulfate-reducing operon coding for a membrane-associated electron transport chain which contains proteins potentially capable of ligating iron-sulfur clusters and heme [8].
• NrfH from this mutant was shown by matrix-assisted laser desorption/ionization mass spectrometry to carry four covalently bound heme groups like wild-type NrfH indicating that the cytochrome c biogenesis system II organism W. succinogenes is able to attach heme to an SXXCH motif [9].

Anatomical context of HEME

• Notably, the N(2)O reductase pre-protein is synthesized with a Sec-dependent signal peptide, rather than the usually observed twin-arginine signal sequence, implying that the copper and heme cofactors are both incorporated in the periplasm [10].

Associations of HEME with chemical compounds

• Adding cyanide to the CO complex of nitrite reductase showed that the two ligands have distinct heme binding sites [11].
• This remaining heme b could be completely reduced by quinone supporting the view that the menaquinone reduction site is located near the distal heme b group [5].
• These results support a functional role of the distal heme ring C propionate in the context of the proposed E-pathway hypothesis of coupled transmembrane electron and proton transfer [12].
• The labeling was achieved by creating a W. succinogenes mutant that was auxotrophic for the heme-precursor 5-aminolevulinate and by providing [1-(13)C]-5-aminolevulinate to the medium [12].
• A rhombic heme Fe(III) EPR signal at g(z) = 2.91, g(y) = 2.3, g(x) = 1.5 titrated with E(m) = -37 mV and is likely to arise from bis-His coordinated heme (heme 2) in which the interplanar angle of the imidazole rings is 21 [13].

Analytical, diagnostic and therapeutic context of HEME

• The tagged HydC, separated from HydAB by isoelectric focusing, was shown to contain 1.9 mol of heme b/mol of HydC demonstrating that HydC ligates both heme b groups [5].
• Probing heme propionate involvement in transmembrane proton transfer coupled to electron transfer in dihemic quinol:fumarate reductase by 13C-labeling and FTIR difference spectroscopy [12].
• Using site-directed mutagenesis, each of the four histidine residues that are predicted to serve as the axial heme ligands in FrdC (His44, His93, His143, and His182) was replaced by alanine or other residues [14].

References