Issue 35, 2019

In vivo methylation of OLA1 revealed by activity-based target profiling of NTMT1

Abstract

N-Terminal methyltransferase 1 (NTMT1) catalyzes the N-terminal methylation of proteins with a specific N-terminal motif after methionine removal. Aberrant N-terminal methylation has been implicated in several cancers and developmental diseases. Together with motif sequence and signal peptide analyses, activity-based substrate profiling of NTMT1 utilizing (E)-hex-2-en-5-ynyl-S-adenosyl-L-methionine (Hey-SAM) revealed 72 potential targets, which include several previously confirmed ones and many unknowns. Target validation using normal and NTMT1 knock-out (KO) HEK293FT cells generated by CRISPR-Cas9 demonstrated that Obg-like ATPase 1 (OLA1), a protein involved in many critical cellular functions, is methylated in vivo by NTMT1. Additionally, Hey-SAM synthesis achieved ≥98% yield for SAH conversion.

Graphical abstract: In vivo methylation of OLA1 revealed by activity-based target profiling of NTMT1

Supplementary files

Article information

Article type
Edge Article
Submitted
24 May 2019
Accepted
08 Aug 2019
First published
09 Aug 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 8094-8099

In vivo methylation of OLA1 revealed by activity-based target profiling of NTMT1

K. Jia, G. Huang, W. Wu, R. Shrestha, B. Wu, Y. Xiong and P. Li, Chem. Sci., 2019, 10, 8094 DOI: 10.1039/C9SC02550B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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