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Heme-iron utilization by Leptospira interrogans requires a heme oxygenase and a plastidic-type ferredoxin-NADP(+) reductase. | LitMetric

Heme-iron utilization by Leptospira interrogans requires a heme oxygenase and a plastidic-type ferredoxin-NADP(+) reductase.

Biochim Biophys Acta

Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Ocampo y Esmeralda, 2000 Rosario, Argentina. Electronic address:

Published: November 2014

AI Article Synopsis

  • Heme oxygenase in Leptospira interrogans converts heme into iron, carbon monoxide, and biliverdin, playing a key role in the bacteria's virulence.
  • A study showed that LepFNR, a specific enzyme type, provides necessary electrons for this process without involving ferredoxin, leading to complete heme degradation and production of free iron and α-biliverdin.
  • Understanding this unique heme degradation pathway could be significant for developing new therapies targeting iron utilization in pathogens like Leptospira.

Article Abstract

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 (1)H 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.

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Source
http://dx.doi.org/10.1016/j.bbagen.2014.07.021DOI Listing

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