# Redox Cofactor Diversity in Enzymatic Superfamilies

> **NIH NIH R35** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $495,000

## Abstract

PROJECT ABSTRACT
Nature has mastered the ability to use bioavailable metals to achieve spectacular transformations of chemistry,
by combining them with diverse protein folds, and unique coordination environments. Through the assembly of
metalloproteins and metalloenzymes, Nature has achieved remarkable diversity in chemical transformations
and in tuning the nascent properties of metal ions such as iron, through generating yet-further-modifiable
redox-active cofactors, like iron-sulfur clusters and iron bound in heme cofactors. To achieve that diversity,
specific protein scaffolds and arrangements of iron-sulfur clusters, and/or heme groups have been elaborated
upon extensively, giving us diverse chemistry — much of which, the fields of enzymology and bioinorganic are
still discovering today. Two NIGMS funded research areas ongoing in the Elliott Group at Boston University
are (1) Query the structure-function relationships of the vast, “AdoMet Radical Enzyme (ARE) superfamily”,
where tens of thousands of reactions are thought to be catalyzed by hundres of thousands of distinct members
of the ARE, through the study of the redox traits of the iron sulfur clusters found in the ARE superfamily; and
(2) Test hypotheses about structural and chemical diversity found with heme containing enzymes of the so-
called “bacterial cytochrome c peroxidase (bCCP) superfamily” found within gram negative micro-organisms.
Through these two related projects, which form the background of the current R35 proposal, the diversity of
structures, function and redox chemistries of metalloproteins are examined through a combination of
electrochemical, biophysical, bioinformatic, and structural approaches. The mechanistic details of the ARE
superfamily are still forthcoming, where many novel states of iron-sulfur clusters have been proposed; here we
will bring our electrochemical lens to bear upon the nature of those states, in order to understand the
thermodynamics and kinetics of their generation and inter-conversion. With respect to the bCCP superfamily,
we have recently demonstrated that novel forms of reactivity of enzymes of this superfamily can be found by
looking beyond the canonical family members that have been examined for the past 20 years. Here we
propose to examine other new family members that are suggested to engage in sulfur-conversions relevant to
the microbiome and to human health. Together, these studies marry our interests in bioinformatics and
biophysical chemistry, to probe the diversity of nature's redox enzymes, revealing not only what is possible in
the chemistry of these remarkable catalysts, but how nature masters the desired reactivity with the correct
metallocofactor.

## Key facts

- **NIH application ID:** 10411899
- **Project number:** 5R35GM136294-03
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** SEAN J ELLIOTT
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $495,000
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411899

## Citation

> US National Institutes of Health, RePORTER application 10411899, Redox Cofactor Diversity in Enzymatic Superfamilies (5R35GM136294-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10411899. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*