# Project 1: Structure, function, and inhibition of SEDS-family peptidoglycan polymerases

> **NIH NIH U19** · HARVARD MEDICAL SCHOOL · 2022 · $754,286

## Abstract

PROJECT SUMMARY
Project 1: Structure, function, and inhibition of SEDS-family peptidoglycan polymerases
The peptidoglycan cell wall is essential for viability and growth in nearly all bacteria, and drugs that interfere with
cell wall assembly are among the most effective antibiotics. Building a peptidoglycan cell wall requires glycan
strand elongation catalyzed by glycosyltransferase enzymes and peptide crosslinking catalyzed by penicillin-
binding proteins (PBPs). In Project 1, we will investigate a newly discovered family of integral membrane
peptidoglycan glycosyltransferase enzymes called shape, elongation, division and sporulation (“SEDS”)
proteins. Proteins in the SEDS family are found in all bacteria with a peptidoglycan cell wall and they are essential
for growth, making them ideal antibiotic targets. In this project, we will investigate SEDS protein function using a
combination of structural biology and chemical biology approaches. Specifically, we will investigate 1) how SEDS
proteins are allosterically activated by PBPs and catalyze peptidoglycan synthesis, 2) how a prototypical SEDS
protein functions in the context of a large multi-protein cell elongation machine called the Rod complex, and 3)
how SEDS proteins are organized and regulated in the divisome cell division machinery. Collectively, this project
will lead to the development of a detailed mechanistic understanding of SEDS protein function as well as the
discovery of new chemical inhibitors of this important protein class.

## Key facts

- **NIH application ID:** 10169873
- **Project number:** 1U19AI158028-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Andrew Kruse
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $754,286
- **Award type:** 1
- **Project period:** 2022-09-07 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169873

## Citation

> US National Institutes of Health, RePORTER application 10169873, Project 1: Structure, function, and inhibition of SEDS-family peptidoglycan polymerases (1U19AI158028-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10169873. Licensed CC0.

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