Nitrite binding to myoglobin and hemoglobin: Reactivity and structural aspects

Area of Science:

• Biochemistry
• Physiology

Background:

• Nitrite (NO2-) is a molecule with significant biological roles.
• Myoglobin (Mb) and hemoglobin (Hb) are heme proteins crucial for oxygen transport and storage.

Purpose of the Study:

• To elucidate the interaction mechanisms between nitrite and different redox states of myoglobin and hemoglobin.
• To explore the structure-function relationships governing nitrite binding to heme proteins.

Main Methods:

• The study discusses the binding modes of nitrite to ferrous and ferric myoglobin and hemoglobin.
• It examines the redox processes involved in nitrite-heme protein interactions.
• Site-directed mutagenesis (HisE7 to Val) was used to probe binding mechanisms.

Main Results:

• Nitrite binds to ferric Mb/Hb forming stable complexes.
• Nitrite binding to ferrous Mb/Hb initiates a redox reaction, reducing nitrite to nitric oxide (NO) and oxidizing the heme protein.
• This redox reaction is vital for endogenous NO production, impacting blood flow and oxygen delivery.
• Nitrite also oxidizes oxygenated Mb/Hb through a complex mechanism.
• The binding mode (O-nitrito vs. N-nitro) is influenced by heme pocket residues.

Conclusions:

• Nitrite's interaction with Mb and Hb is multifaceted, involving both ligand binding and redox reactions.
• The redox interaction is critical for physiological NO generation.
• Heme protein structure, particularly residues near the heme, dictates nitrite binding modes and subsequent functional outcomes.