- Heme-iron utilization by Leptospira interrogans requires a heme oxygenase and a plastidic-type ferredoxin-NADP+ reductase
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Background Heme oxygenase catalyzes the conversion of heme to iron, carbon monoxide and biliverdin employing oxygen and reducing equivalents. This enzyme is essential for heme-iron utilization and contributes to virulence in Leptospira interrogans. Methods A phylogenetic analysis was performed using heme oxygenases sequences from different organisms including saprophytic and pathogenic Leptospira species. L. interrogans heme oxygenase (LepHO) was cloned, overexpressed and purified. The structural and enzymatic properties of LepHO were analyzed by UV-vis spectrophotometry and 1H NMR. Heme-degrading activity, ferrous iron release and biliverdin production were studied with different redox partners. Results A plastidic type, high efficiently ferredoxin-NADP+ reductase (LepFNR) provides the electrons for heme turnover by heme oxygenase in L. interrogans. This catalytic reaction does not require a ferredoxin. Moreover, LepFNR drives the heme degradation to completeness producing free iron and α-biliverdin as the final products. The phylogenetic divergence between heme oxygenases from saprophytic and pathogenic species supports the functional role of this enzyme in L. interrogans pathogenesis. Conclusions Heme-iron scavenging by LepHO in L. interrogans requires only LepFNR as redox partner. Thus, we report a new substrate of ferredoxin-NADP+ reductases different to ferredoxin and flavodoxin, the only recognized protein substrates of this flavoenzyme to date. The results presented here uncover a fundamental step of heme degradation in L. interrogans. General significance Our findings contribute to understand the heme-iron utilization pathway in Leptospira. Since iron is required for pathogen survival and infectivity, heme degradation pathway may be relevant for therapeutic applications.
- Soldano, Anabel,Yao, Huili,Rivera, Mario,Ceccarelli, Eduardo A.,Catalano-Dupuy, Daniela L.
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p. 3208 - 3217
(2014/12/10)
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- SYNTHESIS OF BILIVERDIN IXγ (PTEROBILIN)
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Condensation of a bis(acetoxyethyl)pyrromethane dicarboxylic acid (11d) with a diformylpyrroketone (12b) afforded a bis(acetoxyethyl)-γ-meso-hydroxyporphyrin (13d) which was converted into the related bis(chloroethyl)-γ-benzoyloxyporphyrin (14f).The Zn complex of the latter was transformed by brief treatment with base, followed by chloromethylethyl ether into the zinc bis(chloroethyl)-γ-ethoxymethoxyporphyrin (20b).Dehydrochlorination with potassium t-butoxide in t-butanol, and acid catalysed demetallation and deprotection then afforded the somewhat unstable blue γ-oxyprotoporphyrin dimethyl ester (21).The Fe-complex of the latter readily underwent oxidative ring opening by aerial oxidation in pyridine, and after demetallation gave biliverdin IXγ (pterobilin) dimethyl ester (22).
- Jackson, Anthony H.,Jenkins, Rhianydd M.,Jones, D. Michael,Matlin, Stephen A.
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p. 1849 - 1858
(2007/10/02)
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- Synthesis of the Four meso-Oxyprotoporphyrin Isomers
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The four isomers of meso-oxyprotoporphyrin dimethyl esters have been prepared via direct oxidation of protoporphyrin IX dimethyl ester, separated by h.p.l.c., and identified by conversion into the corresponding biliverdins.
- Jackson, Anthony H.,Rao, K. R. Nagaraja,Wilkins, Martyn
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p. 794 - 796
(2007/10/02)
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- Synthesis of γ-Oxyprotoporphyrin IX and Pterobiline (Biliverdin IXγ)
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The γ-meso-hydroxy-derivative of protoporphyrin IX has been synthesised by condensation of a bis(formylpyrrolyl) ketone and a dipyrrolylmethane; the iron complex underwent oxidative ring-opening to give biliverdin IXγ (pterobiline), the blue-green butterfly pigment, thus providing a model for its biosynthesis.
- Jackson, Anthony H.,Jenkins, Rhiannydd M.,Jones, D. Michael,Matlin, Stephen A.
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p. 763 - 764
(2007/10/02)
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