# Unraveling the dynamics that enable unusual heme enzyme reactivity

> **NIH NIH R35** · EMORY UNIVERSITY · 2023 · $85,000

## Abstract

ABSTRACT
Enzymes are crucial biological catalysts that expedite challenging reactions across all domains
of life. While the development of structural biology methods over the past century has enabled
visualization of these fascinating systems, our understanding of the dynamic processes that
facilitate enzyme reactivity remains limited due to the timescales on which they occur. The
overarching goal in my research group is to develop and apply time-resolved methods capable of
visualizing these processes to elucidate the mechanisms of metal-containing enzymes important
for human health and medicine. Heme-dependent enzymes are of particular interest due to their
role in aerobic metabolism ranging from signal transduction, antibiotic biosynthesis and immune
response. Despite sharing similar structural motifs and catalytic intermediates, heme-dependent
enzymes are capable of catalyzing a wide range of reactions beyond their archetypal
hydroxylation outcomes. This project aims to investigate the structural features and dynamic
behavior that enables this atypical reactivity from dioxygenation to nitration and beyond. In
particular, we plan to repurpose biochemical tools capable of pausing turnover, such as
substrate/cofactor analogs and site-directed mutagenesis, as well as apply state-of-the-art time-
resolved methods that my group is currently developing, to visualize short-lived catalytic
intermediates via a combination of X-ray crystallographic and spectroscopic approaches.
Although applied to specific systems herein, the proposed methodologies may have utility in the
study of heme-enzymes more broadly, as well as other metalloenzymes. Likewise, the anticipated
results have the potential to impact both biocatalysis and the downstream development of
biotechnologies and therapeutics in the treatment of cancers and infectious diseases.

## Key facts

- **NIH application ID:** 10798604
- **Project number:** 3R35GM147557-01S2
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Katherine Marie Davis
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $85,000
- **Award type:** 3
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798604

## Citation

> US National Institutes of Health, RePORTER application 10798604, Unraveling the dynamics that enable unusual heme enzyme reactivity (3R35GM147557-01S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10798604. Licensed CC0.

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