Computational insight into nitration of human myoglobin

Area of Science:

• Biochemistry
• Structural Biology
• Computational Chemistry

Background:

• Protein nitration is a key post-translational modification impacting protein structure and function.
• Heme proteins, like myoglobin (Mb), are particularly sensitive to nitration.
• Experimental structural data for nitrated heme proteins are scarce.

Purpose of the Study:

• To investigate the structural and dynamic effects of sequential protein nitration on human myoglobin.
• To compare the molecular dynamics of nitrated myoglobin variants with native myoglobin.
• To provide atomic-level insights into the structure-function relationship of nitrated heme proteins.

Main Methods:

• Molecular dynamics simulations were employed.
• Human myoglobin was studied with successive nitration at Tyr103, Tyr146, Trp7, and Trp14 residues.
• Analysis focused on protein motions, intramolecular contacts, and internal cavities.

Main Results:

• Nitration of Tyr103 and Tyr146 caused minor alterations to the heme active site conformation.
• Subsequent nitration of Trp7 and Trp14 resulted in helix A shifting away from the protein core.
• This shift led to altered internal cavities and the formation of a water channel, indicating early-stage unfolding.

Conclusions:

• Computational modeling offers valuable atomic-level understanding of protein nitration effects.
• Nitration-induced structural changes in myoglobin provide insights into heme protein behavior in non-native states.
• The study highlights the potential for nitration to disrupt protein structure and function.