Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyanobacteria, red algae, and cryptophytes contain phycobiliproteins which function as photosynthetic light-harvesting pigments. The chromophores of phycobiliproteins are phycobilins, open-chain tetrapyrroles that are synthesized from protoheme. The first step of phycobilin formation is the conversion of protoheme to biliverdin IX alpha in a reaction that is catalyzed by heme oxygenase. In the unicellular red alga, Cyanidium caldarium, light is required for the accumulation of phycobiliproteins. It has been reported previously that the synthesis of the apoprotein components of allophycocyanin and phycocyanin is induced by light in C. caldarium, that the phycobilin precursors, delta-aminolevulinic acid (ALA), protoporphyrin IX, and protoheme can substitute for light, and that the regulation is exerted at the level of mRNA synthesis. We have determined that a key enzyme of phycobilin formation is induced by light in C. caldarium. Extractable heme oxygenase activity is low in dark-grown cells, and it increases approximately 6-fold during the first 24 h after the cells are illuminated. After 24 h, the activity decreases to a level approximately equal to the initial activity. Heme oxygenase is induced in unilluminated cells by administration of ALA. D-Glucose, which is known to inhibit phycocyanin accumulation in C. caldarium, inhibits the induction of heme oxygenase by light or ALA. Induction of heme oxygenase by light or ALA is blocked by cycloheximide, an inhibitor of cytoplasmic protein synthesis, but not by chloramphenicol, an inhibitor of chloroplast protein synthesis. Rifampicin, an inhibitor of algal chloroplast RNA synthesis, and gabaculine, a competitive inhibitor of ALA biosynthesis, block the induction of heme oxygenase by light but not by ALA. These results indicate that heme oxygenase in C. caldarium is induced by phycobilin precursors. The induction by light and the repression of the induction by D-glucose are probably indirect effects mediated by the effects of light and D-glucose on phycobilin precursor formation. The results also indicate that heme oxygenase is encoded by a nuclear gene and is synthesized on cytoplasmic ribosomes.
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PMID:Regulation of heme oxygenase activity in Cyanidium caldarium by light, glucose, and phycobilin precursors. 814 49

Plesiomonas shigelloides is an intestinal pathogen that uses heme as an iron source. The P. shigelloides heme utilization system consists of 10 genes, 7 of which permit heme transport and 3 of which are associated with utilization of heme as an iron source once it is inside the cell. The goal of this study was to examine hugZ, 1 of the 3 genes associated with utilization of heme iron. DPH8, a hugZ mutant, failed to grow to full cell density in media containing heme as the iron source, indicating that hugZ is required for heme iron utilization. Western blots using antibodies against Vibrio cholerae HutZ to detect the P. shigelloides HugZ indicated that hugZ encodes an iron-regulated cytoplasmic protein, which is absent in DPH8. A heme affinity bead assay performed on soluble protein fractions from P. shigelloides DPH8/pHUG24.5 (pHUG24.5 encodes hugZ) indicated that HugZ binds heme. Heme utilization was restored in DPH8 by hox1, which encodes the alpha-heme oxygenase from Synechocystis sp. strain PCC6803. However, HugZ did not exhibit alpha-heme oxygenase activity in an assay that detects the conversion of heme to the bilin functional group present in phycobiliproteins. These results do not rule out that HugZ exhibits another type of heme oxygenase activity not detected in the assay.
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PMID:Plesiomonas shigelloides hugZ encodes an iron-regulated heme binding protein required for heme iron utilization. 1838 78

Iron, an essential nutrient with limited bioavailability, requires specialized cellular mechanisms for uptake. Although iron uptake into the cytoplasm in the form of heme has been well characterized in many bacteria, the subsequent trafficking is poorly understood. The cytoplasmic heme-binding proteins belong to a structurally related family thought to have evolved as "induced fit" ligand-binding macromolecules. One member, Pseudomonas aeruginosa cytoplasmic protein (PhuS), has previously been shown to be important for delivering heme to the iron regulated heme oxygenase (HemO). Spectroscopic investigations of the holo-PhuS complex revealed a dynamic heme environment with overlapping but distinct heme-binding sites with alternative coordinating heme ligands, His-209 or His-212. In the present work we establish a mechanism for how heme is transferred from PhuS to its partner, HemO. Using surface plasmon resonance and isothermal titration calorimetry, we have discovered that holo-PhuS, but not apo-PhuS, forms a 1:1 complex with HemO. Sedimentation velocity and limited proteolysis experiments suggest that heme binding to PhuS induces a conformational rearrangement that drives the protein interaction with HemO. Hydrodynamic analysis reveals that the holo-PhuS displays a more expanded hydrodynamic envelope compared with apo-PhuS, and we propose that this conformational change drives the interaction with HemO. We further demonstrate that replacement of His-212 by Ala disrupts the interaction of holo-PhuS with HemO; in contrast, the His-209-Ala variant can still complex with HemO, albeit more weakly. Together, the present studies reveal a mechanism that couples a heme-dependent conformational switch in PhuS to protein-protein interaction, the subsequent free energy of which drives heme release to HemO.
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PMID:Induced fit on heme binding to the Pseudomonas aeruginosa cytoplasmic protein (PhuS) drives interaction with heme oxygenase (HemO). 2245 25