Nitrosative stress and NO detoxifying reaction mechanisms in microbial nonheme diiron proteins

NIH RePORTER · NIH · R01 · $323,400 · view on reporter.nih.gov ↗

Abstract

PROJECT SUMMARY Metalloenzymes play crucial roles throughout human health and govern the biochemistry of dioxygen (O2) and nitric oxide (NO). Pathogenic organisms depend on heme and nonheme iron-containing proteins to counter the human immune response and to survive exposure to high concentrations of reactive oxygen and nitrogen species (ROS/RNS). The Moënne-Loccoz Lab combines classic biochemical techniques, resonance Raman (RR), FTIR, and EPR spectroscopies with time-resolved techniques to probe microbial enzymatic systems characterized by X-ray crystallography, but with catalytic strategies that remain poorly understood or totally unknown. In this project, a recent crystal structure of a novel mycobacterial diiron protein upregulated upon macrophage infection is targeted for investigation after showing unique structural features and reactivity toward RNS never seen before in biology or inorganic chemistry.

Key facts

NIH application ID
10810778
Project number
5R01GM147588-02
Recipient
OREGON HEALTH & SCIENCE UNIVERSITY
Principal Investigator
PIERRE MOENNE-LOCCOZ
Activity code
R01
Funding institute
NIH
Fiscal year
2024
Award amount
$323,400
Award type
5
Project period
2023-04-01 → 2027-02-28