Disease relevance of HEM2

• The crystal structure of the Mg2+-dependent PBGS from the human pathogen Pseudomonas aeruginosa in complex with the competitive inhibitor levulinic acid (LA) solved at 1.67 A resolution shows a homooctameric enzyme that consists of four asymmetric dimers [1].

High impact information on HEM2

• These mutations are leaky versions of HEM2 and HEM4, respectively; addition of exogenous hemin reverses the suppressing effects of slu1 and slu2 [2].
• Characterization of the yeast HEM2 gene and transcriptional regulation of COX5 and COR1 by heme [3].
• A gene capable of complementing the respiratory deficiency of C41 and N28 has been cloned by transformation of a hem2 mutant with a recombinant plasmid library of wild type yeast nuclear DNA [3].
• The mutants are unable to convert delta-aminolevulinic acid to porphobilinogen and are not complemented by the hem2 mutant GL4 (Gollub, E. G., Liu, K.-P., Dagan, J., Adlersberg, M., and Sprinson, D. B. (1977) J. Biol. Chem. 252, 2846-2854) [3].
• Mutants in hem1, hem2, and hem3 had an additional requirement for methionine on synthetic medium supplemented with either heme or ergosterol and Tween 80, owing to a lack of sulfite reductase which contains siroheme, a modified uroporphyrin III [4].

Biological context of HEM2

• Saccharomyces cerevisiae transformed with a multicopy plasmid carrying the yeast structural gene HEM2, which codes for delta-aminolevulinate dehydratase, was enriched 20-fold in the enzyme [5].
• The cloned gene showed high levels of nucleic acid and protein sequence homology to the HEM2 genes, encoding porphobilinogen synthases, from several sources [6].
• Curing transformed cells of plasmid restored the hem2 mutant phenotype [7].

Associations of HEM2 with chemical compounds

• A role for HEM2 in cadmium tolerance [6].
• Levulinic acid, a competitive inhibitor of delta-aminolevulinic acid dehydratase, was used to inhibit cytochrome biosynthesis in growing yeast cells [8].

References