# Mapping the structural basis for mechanistic diversity in metalloenzyme superfamilies

> **NIH NIH R35** · PENNSYLVANIA STATE UNIVERSITY, THE · 2021 · $421,268

## Abstract

Project Summary
Enzymes that employ transition metals can initiate chemically challenging modifications
of inert chemical bonds. These systems serve as both important drug targets and useful
biocatalysts. In certain transition-metal driven essential biological transformations, such
as DNA biosynthesis, divergent trace elements can be used for reaction initiation.
Discovery of novel metal cofactors used for these processes, and their mechanisms of
assembly and deployment, will enable novel routes of enzyme inhibition in bacterial
pathogens. In a second project, structures and reaction mechanisms in three different
metalloenzyme superfamilies relevant to biocatalysis will be elucidated. These systems
use a common cofactor to catalyze divergent reaction outcomes, controlled by structural
features of each enzyme. A comparative approach provides detailed and testable
hypotheses about the means by which distinct chemical reactions are accomplished, as
well as discovery of entirely new families of enzymes and new ways to control their
activities. The objective of this work is to enable exploitation of the catalytic power
inherent in these systems for more efficient and environmentally friendly synthesis of
drugs, chemicals, technological tools, and new chemical processes.

## Key facts

- **NIH application ID:** 10201240
- **Project number:** 2R35GM119707-06
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** Amie K Boal
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $421,268
- **Award type:** 2
- **Project period:** 2016-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201240

## Citation

> US National Institutes of Health, RePORTER application 10201240, Mapping the structural basis for mechanistic diversity in metalloenzyme superfamilies (2R35GM119707-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201240. Licensed CC0.

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