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Updated: Jul 18, 2026
12:07
Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Crystal structure and functional analysis of the histone methyltransferase SET7/9
Jonathan R Wilson1, Chun Jing, Philip A Walker
1Structural Biology Group, National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom.
Cell
|October 10, 2002
Summary
Histone methylation regulates chromatin structure. Researchers elucidated the crystal structure of human SET7/9, identifying key residues for histone H3 lysine-4 methylation and cofactor binding.
Area of Science:
- Biochemistry
- Structural Biology
- Epigenetics
Background:
- Histone methylation is crucial for regulating chromatin structure.
- The SET domain is common in histone lysine methyltransferases.
Purpose of the Study:
- To determine the crystal structure of a human SET7/9 fragment.
- To identify residues essential for histone H3 lysine-4 methylation.
- To understand cofactor (AdoMet) binding and catalytic mechanisms.
Main Methods:
- X-ray crystallography of human SET7/9 fragment.
- Site-directed mutagenesis.
- Biochemical assays for enzyme activity and substrate interaction.
Main Results:
- The crystal structure revealed N-terminal beta-sheet and SET domains.
- Two C-terminal residues were identified as essential for catalytic activity on histone H3 lysine-4.
- The binding mode of the cofactor AdoMet was elucidated.
- Invariant residues' roles in catalysis, AdoMet binding, and substrate interaction were supported by biochemical data.
Conclusions:
- The study provides structural and biochemical insights into SET7/9 function.
- Understanding SET7/9 mechanism aids in comprehending epigenetic regulation.
- This work may inform the development of targeted therapeutics.
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