# Structural insights into the functional regulation of O-GlcNAcase

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $328,421

## Abstract

Human O-GlcNAcase (OGA) is the sole enzyme that hydrolyzes O-GlcNAcylation, an essential intracellular
protein glycosylation that functionally regulates thousands of proteins in response to nutrients and stress.
Aberrant functions of OGA have been detected in numerous diseases including cancer and neurodegeneration,
fostering intense interest in OGA as a therapeutic target. However, due to the lack of complete OGA structure
and the paucity of information on its substrate recognition, little is known about how OGA can accommodate
such a broad range of substrates without a consensus sequence motif, while still maintaining certain level of
specificity. Our preliminary studies provide strong evidence suggesting that OGA’s non-catalytic regions play
critical roles in substrate binding and new functions that we are just beginning to reveal. We propose to advance
structural and functional investigation of OGA. The new findings from this study will help decode OGA’s complex
cellular regulation and will serve as a critical foundation for manipulating the precise role of OGA, paving the way
for development of more effective and safer therapies for challenging diseases.

## Key facts

- **NIH application ID:** 10825240
- **Project number:** 1R01GM152998-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Jiaoyang Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $328,421
- **Award type:** 1
- **Project period:** 2024-02-15 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825240

## Citation

> US National Institutes of Health, RePORTER application 10825240, Structural insights into the functional regulation of O-GlcNAcase (1R01GM152998-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10825240. Licensed CC0.

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