# Substrate Channeling and Communication in Proline Metabolic Enzymes

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2024 · $442,340

## Abstract

PROJECT SUMMARY
Metabolic enzymes in cells rarely function in isolation. Often their activities are coordinated by physical or
covalent association with each other and cellular structures. A consequence of these associations is that
metabolic intermediates do not equilibrate with the cellular milieu and are instead channeled between
enzyme active sites. Despite the widespread recognition that protein-protein interactions are ubiquitous,
the molecular mechanisms of substrate channeling remain obscure, and the impact of channeling at the
cellular and organismal levels is largely unknown. We seek to narrow these knowledge gaps by exploring
substrate channeling within and between the enzymes of proline catabolism. The proposed experiments
will explore long-distance, allosteric communication between the active sites of the bifunctional enzyme
PutA using kinetic crystallography, assess the contributions of substrate channeling to bacterial fitness
and pathogenesis, and determine the first structure of a novel bifunctional enzyme that moonlights as a
transcriptional repressor using cryo-EM.

## Key facts

- **NIH application ID:** 10846645
- **Project number:** 5R01GM065546-14
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Donald F Becker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $442,340
- **Award type:** 5
- **Project period:** 2002-05-05 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10846645

## Citation

> US National Institutes of Health, RePORTER application 10846645, Substrate Channeling and Communication in Proline Metabolic Enzymes (5R01GM065546-14). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10846645. Licensed CC0.

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