# Structural Characterization of Gbetagamma-Phospholipase C complexes

> **NIH NIH F32** · PURDUE UNIVERSITY · 2022 · $67,582

## Abstract

PROJECT SUMMARY
The opioid crisis, cardiovascular disease, and cancer are the most pressing healthcare crises in
the United States. PLCβ enzymes are essential for normal analgesic, cardiovascular, and
proliferative signaling. Further, disruption of interactions between PLCβ and its G protein
activators have been shown to improve outcomes in preclinical models of opioid induced
analgesia, cardiac hypertrophy, and cancer. However, targeting these interactions specifically is
nearly impossible in the absence of structural data that informs on the conformational differences
between inactive, active, and G protein bound PLCβ states. The goal of this project is to
understand mechanisms of PLCβ activation by Gβγ and/or the membrane through structural and
functional studies. The Gβγ binding site on PLCβ has yet to be defined, and overall, Gβγ-
dependent regulation of effector enzymes is a poorly understood process. This project would not
only increase our overall understanding of PLCβ signaling at the membrane and in conjunction
with Gβγ but would also provide insights into the regulation of other enzymes that act at the
membrane interface. The completion of this study will synergistically increase our understanding
of PLCβ activation mechanisms, providing insights that can be leveraged for the development of
probes, and ultimately potential therapeutics, targeting G protein–PLCβ interactions.

## Key facts

- **NIH application ID:** 10389848
- **Project number:** 1F32GM145110-01
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** ISAAC FISHER
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 1
- **Project period:** 2022-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389848

## Citation

> US National Institutes of Health, RePORTER application 10389848, Structural Characterization of Gbetagamma-Phospholipase C complexes (1F32GM145110-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10389848. Licensed CC0.

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