# Exploring the protein structural features which regulate myoglobin's proton transfer dependent high-valent auto-reduction

> **NIH NIH SC2** · XAVIER UNIVERSITY OF LOUISIANA · 2022 · $142,000

## Abstract

The goal of this study is to understand the mechanisms of the auto-reduction of high-
valent iron species in two different myoglobin species, horse heart and human, in order
to uncover the structural features that regulate the corresponding oxidative protein
damage. Myoglobin’s propensity to oxidatively damage lipoproteins is a particular
interest in the molecular mechanism of atherosclerosis. The hypothesis is that proton
and electron movements that regulate the auto-reduction can inform how we study
oxidative damage in proteins and atherogenic lipoproteins. To test this assumption, the
mechanism will be evaluated by determining three different features. The first aim will
focus on probing the kinetic and thermodynamic parameters of the auto-reduction
reaction for both Mb species using transient UV-visible absorbance spectroscopy and
by varying temperature and pH conditions. The second aim is to identify the proton
source necessary for auto-reduction of the high-valent iron species and determine if one
or more different protons are important in regulating the mechanism at physiologically
low pH (inflammation sites) and neutral pH(blood based environments) utilizing kinetic
solvent isotope effects, proton inventories, and site directed mutagenesis. The third aim
focuses on identifying the electron donor source within the protein utilizing radical traps,
tandem mass spectrometry and cyclic voltammetry.

## Key facts

- **NIH application ID:** 10436167
- **Project number:** 5SC2GM136557-03
- **Recipient organization:** XAVIER UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Heather Rebecca Williamson
- **Activity code:** SC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $142,000
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436167

## Citation

> US National Institutes of Health, RePORTER application 10436167, Exploring the protein structural features which regulate myoglobin's proton transfer dependent high-valent auto-reduction (5SC2GM136557-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10436167. Licensed CC0.

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