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Updated: Jan 22, 2026
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Specificity Analysis of Protein Lysine Methyltransferases Using SPOT Peptide Arrays
Published on: November 29, 2014
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Substrate docking-mediated specific and efficient lysine methylation by the SET domain-containing histone
Haiyang Liu1, Zhiwei Li2, Qingqing Yang2
1Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China.
The Journal of Biological Chemistry
|July 21, 2019
Summary
Lysine methyltransferases (KMTs) like SETD7 use specific docking sites on substrates via MORN repeats for targeted protein methylation. This mechanism explains SETD7
Area of Science:
- Biochemistry
- Molecular Biology
- Epigenetics
Background:
- Lysine methylation is a crucial post-translational modification catalyzed by lysine methyltransferases (KMTs).
- Dysregulation of KMT activity is implicated in various human diseases.
- Specific mechanisms for substrate recognition by KMTs, especially for nonhistone proteins, remain largely unknown.
Purpose of the Study:
- To elucidate the mechanism by which SET domain-containing 7 histone lysine methyltransferase (SETD7) achieves substrate specificity.
- To investigate the role of SETD7's N-terminal MORN repeats in substrate docking and methylation.
Main Methods:
- Analytical gel filtration chromatography
- Isothermal titration calorimetry
- In vitro methylation assays
Main Results:
- SETD7 utilizes its N-terminal MORN repeats to dock substrates.
- This docking positions the lysine methylation motif for efficient catalysis by the SET domain.
- This mechanism explains known SETD7 substrates and predicts novel ones.
Conclusions:
- SETD7 employs a docking site-mediated mechanism for substrate recognition and methylation.
- This mechanism enhances catalytic specificity and efficiency.
- Other KMTs may utilize similar substrate recognition strategies.
Keywords:
MORN repeatsSET domain-containing 7 histone methyltransferase (SETD7)charge-charge interactiondockingdocking interactionenzyme catalysisepigeneticsgene regulationhistone methylationlysine methylationposttranslational modificationprotein methylationprotein-protein interactionsubstrate specificity
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