# Complementary Studies of Native Sulfite Reductase and Biosynthetic Model to Understand Structural Features Responsible for Selective Multi-Electron Reduction of Sulfite

> **NIH NIH F32** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $64,554

## Abstract

Project Summary/Abstract
 The goal of this project is to obtain detailed understanding of the structural features present
in a class of multinuclear metalloenzymes that make it capable of promoting selective 6 e-
reduction of sulfite (SiRs), and address important scientific issues in the fields of complex
multinuclear transition metal active sites and the global sulfur cycle. Specifically, this project seeks
to understand the role of the coupled auxiliary [4Fe-4S] cluster reduction potential on facilitating
efficient—and selective—S-O bond cleavage of sulfite, along with the chemical nature of
intermediates that have been proposed in the catalytic cycle of SiRs. To achieve this goal, this
project proposes complimentary studies, both of a native SiR protein, and a biosynthetic model
capable of catalyzing sulfite reduction—the only current structural and functional model of SiRs.
Using a novel biosynthetic approach, which aims to overcome limitations inherent to studies of
the native enzyme alone, a robust scaffold will be used to learn which features of SiR are crucial
for its activity, through experiments designed to display a gain in function, as opposed to inferring
structure-function relationship through loss of activity in the native enzyme. The proposed
complimentary studies of these two systems will allow us to identify the structural features unique
to SiRs that lead to high catalytic efficiency towards a complex multi-electron, multi-proton
transformation. We will be able to understand: (1) the importance of the redox active [4Fe-4S]
cluster coupled to the siroheme substrate binding site on SiR activity, (2) the nature of postulated
Fe-SOx intermediates, and their relevance to the catalytic cycle of SiR, and (3) the features of the
siroheme ligand in SiR which make it suitable for sulfite reduction activity, relative to the heme c
of the biosynthetic scaffold.
 Achieving the above goals will result in a deeper understanding of the structure and function
of SiRs that may be difficult to achieve by studying the native enzyme alone. By mimicking the
function of a native system through rational modifications with a different protein scaffold,
generalizable conclusions can be made concerning important structural features of the native
active site. This research plan will advance the knowledge of a broad range of multinuclear
metalloenzymes relevant to human health, specifically, related to their structure, function, and
metalloenzyme design in general, while providing an excellent training opportunity to achieve the
career goal the candidate.

## Key facts

- **NIH application ID:** 9911228
- **Project number:** 1F32GM136177-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Christopher (Chris) J Reed
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,554
- **Award type:** 1
- **Project period:** 2020-02-16 → 2023-02-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9911228

## Citation

> US National Institutes of Health, RePORTER application 9911228, Complementary Studies of Native Sulfite Reductase and Biosynthetic Model to Understand Structural Features Responsible for Selective Multi-Electron Reduction of Sulfite (1F32GM136177-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9911228. Licensed CC0.

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