Cellular levels of heme affect the activity of dimeric glutamyl-tRNA reductase

Non-Canonical Heme-Binding Proteins

“…The authors found that heme content in GluTR varied according to the concentration of heme provided in the culture medium, and that heme bound preferentially to the dimeric state of the protein. 92 Variability in heme content for GluTR was reported for two other species, namely C. vibrioforme (1 heme per monomer) 93 and M. tuberculosis (1 heme per 16 monomers) 94 GluTR. Binding of heme was accompanied by the formation of a low-spin complex with a Soret peak maximum appearing at 420 nm.…”

“…GluTR catalyzes the conversion of glutamyl-tRNA into glutamate-1-semialdehyde, a precursor for 5-aminolevulinic acid. 91 De Armas-Ricard et al 92 first showed that recombinant GluTR co-purifies with heme b. The authors found that heme content in GluTR varied according to the concentration of heme provided in the culture medium, and that heme bound preferentially to the dimeric state of the protein.…”

“…Importantly, an inverse correlation was found between heme binding and the catalytic activity, which suggests that heme could act as a cellular modulator for the expression and activity of GluTR. 92 Crystallographic analysis of heme-free GluTR showed that the protein is a homodimer featuring an unusual V-shape structure with three distinct domains (I-III) connected by an α-helix. 95 Information on potential heme-binding sites is lacking, however, it likely involves regions involved in catalysis (domain I) or NADPH binding (domain II) due to the antagonistic effect of heme on the catalytic properties of GluTR.…”

The Alternative Route to Heme in the Methanogenic ArchaeonMethanosarcina barkeri

“…As soon as the demand for heme is satisfied, the cofactor would bind to the AhbAB complex and might possibly inhibit its catalytic activity. Second, heme binding to AhbAB might control protein stability as observed for glutamyl-tRNA reductase which was reported to be inhibited upon heme binding and also seemed to be more amenable to proteolytic degradation in the heme-bound form [22–24]. The eukaryotic 5-aminolevulinic acid synthase (ALAS1) represents another example for a feedback-regulation by heme.…”

Glutamyl-tRNA in Bacteria. Multiple Identities for Multiple Functions

“…79,81 Binding of heme to GluTR has also been shown to in- hibit enzyme activity in A. ferrooxidans GluTR. 68 In this bacterium, modulation of Glu-tRNA Glu synthesis by GluRS1 seems to complement the regulation of GluTR. As A. ferrooxidans produces high levels of heme (up to ≈ 6 times more than E. coli), the control of GluRS1 might be necessary in order to prevent a decrease in Glu-tRNA Glu levels when tetrapyrrole requirements increase.…”