# Structural and functional studies of YbtPQ for fighting bacterial infections

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2023 · $194,375

## Abstract

One of the eternal wars between the host and pathogens is the fight for nutritional metal ions. Bacteria have
evolved multiple pathways to achieve that, including the one mediated by a group of small molecules called
siderophores that are often critical for the virulence of the bacteria. The long-term goal is to help develop potential
molecules targeting the siderophore-mediated metal uptake process, so to treat bacterial infections. However,
one of the critical steps in this process, the substrate uptake mediated by ATP-binding-cassette (ABC) importers,
is poorly understood. The overall objective in this proposal is to address the problem by studying the detailed
molecular mechanism of a specific siderophore ABC importer from uropathogenic Escherichia coli (UPEC): the
yersiniabactin (Ybt) importer YbtPQ. The rational is that, with detailed knowledge gained here, it will be possible
to design and optimize small molecules to specifically target YbtPQ. To accomplish the goal, two specific aims
will be pursued: 1) reconstructing its complete transport cycle by structural studies; and 2) investigating its
substrate selectivity and interaction with potential inhibitors. The multidisciplinary approach used here include
structural biology, biochemistry, biophysics, as well as microbiology. The proposal is innovative because 1)
YbtPQ is an exporter-like importer, representing a substantial departure from the established paradigm of ABC
importers; and 2) the results will provide potential inhibitors against YbtPQ that could be clinically useful in the
future. Last but not least, this study is also significant because it is expected to not only reveal novel molecular
mechanism of exporter-like importer, but also provide scientific justification for further development of drugs
against siderophore ABC importers.

## Key facts

- **NIH application ID:** 10644889
- **Project number:** 1R21AI175646-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Hongjin Zheng
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $194,375
- **Award type:** 1
- **Project period:** 2023-02-17 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10644889

## Citation

> US National Institutes of Health, RePORTER application 10644889, Structural and functional studies of YbtPQ for fighting bacterial infections (1R21AI175646-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10644889. Licensed CC0.

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