Disease relevance of hemA

• The recombinant plasmid carrying the synthetase gene was also able to weakly complement an Escherichia coli hemA mutant [1].
• The hemA gene encoding 5-aminolevulinic acid synthase (ALAS) was cloned from the genomic DNA of photosynthetic bacterium Rhodopseudomonas palustris KUGB306 [2].
• Cloning and characterization of the hemA region of the Bacillus subtilis chromosome [3].
• In the photosynthetic bacterium Rhodobacter sphaeroides, two genes, hemA and hemT, each encode a distinct 5-aminolevulinic acid (ALA) synthase isozyme (E. L. Neidle and S. Kaplan, J. Bacteriol. 175:2292-2303, 1993) [4].
• Conditional stability of the HemA protein (glutamyl-tRNA reductase) regulates heme biosynthesis in Salmonella typhimurium [5].

High impact information on hemA

• The deduced amino acid sequence of the HEMA protein predicts a protein of 60 kD with substantial similarity (30 to 47% identity) to sequences derived from the known hemA genes from microorganisms that make ALA by the C5 pathway [6].
• Aminolevulinate synthase was overexpressed in an active form and, therefore, was able to rescue hemA mutants, which are unable to grow in the absence of 5-aminolevulinate [7].
• A temperature-sensitive mutant of this latter plasmid, which was unable to complement hemA at high temperature, produced enzyme having temperature-sensitive synthetase activity in vitro [1].
• Glutamyl tRNA reductase (GluTR) catalyses the NADPH-dependent reduction of glutamyl tRNA to glutamate 1-semialdehyde [8].
• The sequence of the partial clone, BHA13, contains at least 87 base mismatches in the coding region for the mature GluTR resulting in 11 amino acid substitutions [8].

Chemical compound and disease context of hemA

• Membrane-bound nitrate reductase of Escherichia coli consists of three subunits designated as A, B, and C, with subunit C being the apoprotein of cytochrome b, A hemA mutant that cannot synthesize delta-aminolevulinic acid (ALA) produces a normal, stable, membrane-bound enzyme when grown with ALA [9].
• Sensitivity of hemA mutant Escherichia coli cells to inactivation by near-UV light depends on the level of supplementation with delta-aminolevulinic acid [10].

Biological context of hemA

• Aerobic expression of the hybrid operon was also enhanced in isogenic derivatives of the fusion strains deficient in protoporphyrin biosynthesis (hemA) [11].
• The mutant phenotype was conferred by a lesion at a previously undescribed locus between hemA and trpA, which we have termed pilG [12].

Anatomical context of hemA

• Large scale production of biologically active Escherichia coli glutamyl-tRNA reductase from inclusion bodies [13].

Associations of hemA with chemical compounds

• Induction of expression of hemA by WC1201 was optimized for concentration of inducer (IPTG, 5 mM), temperature (37 degrees C), presence of betaine and sorbitol (no change) and time of induction (2h) [14].
• Cell extract prepared from the hemA strain SASX41B was incapable of producing ALA from either glutamate or glutamyl-tRNA, whereas extract of the hem+ strain HB101 formed colorimetrically detectable amounts of ALA and transferred label from 1-[14C]glutamate and 3,4-[3H]glutamyl-tRNA to ALA [15].
• GTR was observable as a 46 kDa band by Brilliant blue G staining of SDS-PAGE gels [14].

Analytical, diagnostic and therapeutic context of hemA

• Steady-state level of BHA1- and BHA13-specific mRNA encoding GluTR were analysed by Northern blot hybridization using cDNA-specific oligo nucleotides and quantitative reverse transcriptase-polymerase chain reaction [8].
• Autoradiography on native gradient PAGE showed that GTR expressed in vivo by induction of WC1201 had a molecular weight of approx. 117 kDa [14].

References