# Protein N-terminal Methylation Mechanisms and Inhibition

> **NIH NIH R01** · PURDUE UNIVERSITY · 2024 · $307,697

## Abstract

This proposal is a competing renewal application of R01 GM117675 that uses a multidisciplinary approach to
enhance our understanding of protein α-N-terminal methylation. The α-N-terminal methylation plays an
essential role in regulating cell mitosis, chromatin interactions, and DNA repair. Its level is increased as
response of cellular stress, aging, and developmental processes. The increasing occurrences of α-N-terminal
methylation on the canonical X-P-K/R motif and noncanonical motifs highlight the importance of this
underexplored modification. However, there are major gaps remain in our understanding of these fundamental
biological processes. Filling these gaps is essential to elucidate the α-N-terminal methylation-mediated
pathways and to enhance the opportunity to devise novel therapeutic approaches. The objective of this
research is to develop novel chemical tools and apply them to understand the pathway and functions mediated
protein α-N-terminal methylation. Meanwhile, we will elucidate the molecular basis for substrate specificity of
human methyltransferase like 13 that methylates the the eukaryotic elongation factor 1 alpha containing the
new GKEK motif at the α-N-terminus. Taken together, we believe that this research effort has the great
potential to provide a clearer understanding of mechanisms and inhibition of NTMTs, and shed lights on the
biological impact of protein α-N-terminal methylation. Accomplishment of the proposed work will provide new
chemical tools for both basic biology research and has the opportunity to enhance the development of novel
therapeutic approaches to target α-N-terminal methylation-involved pathways.

## Key facts

- **NIH application ID:** 10783096
- **Project number:** 5R01GM117275-08
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Rong Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $307,697
- **Award type:** 5
- **Project period:** 2016-09-20 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10783096

## Citation

> US National Institutes of Health, RePORTER application 10783096, Protein N-terminal Methylation Mechanisms and Inhibition (5R01GM117275-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10783096. Licensed CC0.

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