# Signal Propagation in Protein Allostery: Mechanism and Evolution

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2021 · $323,614

## Abstract

Project Summary/Abstract
 Although its significance for biology has been recognized for more than a
century, the molecular mechanism of allostery remains the subject of intense research.
In allostery a signal from one site in a protein is transmitted to a second, often distant,
site to alter its function. The ensemble model provides a framework in which dynamic
and/or structural changes can contribute to allosteric regulation even within a single
protein. The challenge lies in deciphering which molecular processes are critical to signal
transmission. In this work we will investigate the allosteric mechanism in the Group II
Biotin Protein Ligase, E.coli BirA protein. We hypothesize that BirA allostery occurs
through direct coupling of dynamic changes in multiple loops to formation of residue
networks. We further hypothesize that this mechanism allowed for the evolution of
allostery while preserving an essential enzymatic function in post-translational biotin
addition. These hypotheses will be tested using integrated genetic screening, solution
biophysical measurements, x-ray crystallography, and molecular dynamics simulations.
The elucidation of how allostery works in BirA will improve our general understanding of
allosteric mechanisms and may prove useful for developing drugs that selectively target
specific microbial BPLs and for creating Biotin Protein Ligase-based technology tools.

## Key facts

- **NIH application ID:** 10072061
- **Project number:** 5R01GM129327-03
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** David Joseph Weber
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $323,614
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072061

## Citation

> US National Institutes of Health, RePORTER application 10072061, Signal Propagation in Protein Allostery: Mechanism and Evolution (5R01GM129327-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10072061. Licensed CC0.

---

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