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.

Ascenzi, P., di Masi, A., Leboffe, L., Fanali, G., & Fasano, M. (2017). The drug-dependent five- to six-coordination transition of the heme-Fe atom modulates allosterically human serum heme-albumin reactivity. RENDICONTI LINCEI. SCIENZE FISICHE E NATURALI, 28, 207-215 [10.1007/s12210-016-0562-2].

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

ASCENZI, Paolo;DI MASI, ALESSANDRA;LEBOFFE, LORIS;
2017

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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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11590/322929
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