Kinetic mechanism of protein N-terminal methyltransferase 1.

The Journal of Biological Chemistry
Stacie Lynn RichardsonRong Huang

Abstract

The protein N-terminal methyltransferase 1 (NTMT1) catalyzes the transfer of the methyl group from the S-adenosyl-l-methionine to the protein α-amine, resulting in formation of S-adenosyl-l-homocysteine and α-N-methylated proteins. NTMT1 is an interesting potential anticancer target because it is overexpressed in gastrointestinal cancers and plays an important role in cell mitosis. To gain insight into the biochemical mechanism of NTMT1, we have characterized the kinetic mechanism of recombinant NTMT1 using a fluorescence assay and mass spectrometry. The results of initial velocity, product, and dead-end inhibition studies indicate that methylation by NTMT1 proceeds via a random sequential Bi Bi mechanism. In addition, our processivity studies demonstrate that NTMT1 proceeds via a distributive mechanism for multiple methylations. Together, our studies provide new knowledge about the kinetic mechanism of NTMT1 and lay the foundation for the development of mechanism-based inhibitors.

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Citations

Nov 6, 2015·ACS Chemical Biology·Jing Zhang, Yujun George Zheng
May 31, 2017·Protein Science : a Publication of the Protein Society·Kaitlyn M ShieldsChristine E Schaner Tooley
Nov 28, 2018·Chembiochem : a European Journal of Chemical Biology·Rong Huang
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Jan 14, 2021·International Journal of Molecular Sciences·Yi-Hsun HoRong Huang
Apr 12, 2021·Current Opinion in Chemical Biology·Krystal DiazRong Huang
Mar 19, 2019·Journal of Medicinal Chemistry·Dongxing ChenRong Huang
Aug 31, 2021·RSC Medicinal Chemistry·Iredia D Iyamu, Rong Huang

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