# Mapping the structural basis for mechanistic diversity in metalloenzyme superfamilies

> **NIH NIH R35** · PENNSYLVANIA STATE UNIVERSITY, THE · 2022 · $58,746

## Abstract

Project Summary
The parent grant for this supplement aims to discover novel enzymatic cofactors involved in DNA biosynthesis
in pathogens. The overarching goal is to enable new routes to enzyme inhibition in bacteria that cause infectious
disease. Here we will investigate the mechanism of assembly of an essential tyrosine-derived post-translationally
modified radical cofactor found in a subclass of microbial ribonucleotide reductases through incorporation of non-
native amino acids. This approach will allow us to identify aspects of cofactor assembly that could be targeted
for disruption by therapeutic interventions. In a second aim, we will characterize the cofactor used by this enzyme
subclass in a native host organism. The project as a whole will set the stage for understanding how this enzyme
subclass is used inside the cell, ultimately allow us to test the impact of disruption of cofactor assembly in a
relevant biological context. The project provides an excellent training opportunity for the Ph.D. candidate
supported by the supplement in work at the interface between chemistry and microbiology. A collaborative
mentoring team is in place with expertise in non-native amino acid methodology, structural and biochemical
characterization of proteins, and cultivation of pathogenic and commensal microbes.

## Key facts

- **NIH application ID:** 10598851
- **Project number:** 3R35GM119707-07S1
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** Amie K Boal
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $58,746
- **Award type:** 3
- **Project period:** 2016-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10598851

## Citation

> US National Institutes of Health, RePORTER application 10598851, Mapping the structural basis for mechanistic diversity in metalloenzyme superfamilies (3R35GM119707-07S1). Retrieved via AI Analytics 2026-08-11 from https://api.ai-analytics.org/grant/nih/10598851. Licensed CC0.

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