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The drug-dependent five- to six-coordination transition of the heme-Fe atom modulates allosterically human serum heme-albumin reactivity

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Abstract

Human serum albumin (HSA), the most abundant protein in plasma, displays several functions including heme transfer from high- and low-density lipoproteins to hemopexin; therefore, the HSA-heme complex acquires transiently heme-based (pseudo-)enzymatic properties. In particular, ferric human serum heme-albumin (HSA-heme) and ferrous nitrosylated HSA-heme inactivate peroxynitrite, and ferrous HSA-heme catalyzes the conversion of nitrite to nitrogen monoxide. The (pseudo-)enzymatic properties of HSA-heme are modulated allosterically by endogenous and exogenous ligands, such as drugs. The modulation of ligand binding to plasma proteins is relevant not only under physiological conditions but also in the pharmacological therapy management. Here, drug-dependent HSA-heme properties are reviewed from the functional and structural viewpoints. In particular, the drug-dependent five- to six-coordination transition of the heme-Fe atom is at the root of the allosteric modulation of the HSA-heme reactivity.

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Abbreviations

FA:

Fatty acid

HSA:

Human serum albumin

HSA-heme:

Human serum heme-albumin

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Acknowledgments

The authors wish to thank colleagues as well as past and present members of their laboratories who contributed with data and discussions to the ideas presented here.

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Authors and Affiliations

  1. Interdepartmental Laboratory for Electron Microscopy, Roma Tre University, Via della Vasca Navale 79, 00146, Rome, Italy

    Paolo Ascenzi, Alessandra di Masi & Loris Leboffe

  2. Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, 00146, Rome, Italy

    Alessandra di Masi & Loris Leboffe

  3. Department of Science and High Technology, University of Insubria, Via Luciano Manara 7, 21052, Busto Arsizio, VA, Italy

    Gabriella Fanali & Mauro Fasano

  4. Center of Neuroscience, University of Insubria, 21052, Busto Arsizio, VA, Italy

    Mauro Fasano

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  1. Paolo Ascenzi
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  2. Alessandra di Masi
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  3. Loris Leboffe
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  4. Gabriella Fanali
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  5. Mauro Fasano
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Correspondence to Paolo Ascenzi.

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Ascenzi, P., di Masi, A., Leboffe, L. et al. The drug-dependent five- to six-coordination transition of the heme-Fe atom modulates allosterically human serum heme-albumin reactivity. Rend. Fis. Acc. Lincei 28 (Suppl 1), 207–215 (2017). https://doi.org/10.1007/s12210-016-0562-2

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