Interaction between DNA/histone methyltransferases and their inhibitors

Area of Science:

• Epigenetics and molecular biology
• Drug discovery and medicinal chemistry

Background:

• DNA methylation and histone methylation are key epigenetic mechanisms regulating gene expression and genome function.
• Dysregulation of methyltransferases is implicated in various diseases, notably cancer.
• Inhibition of DNA and histone methyltransferases (DNMTs and HMTs) presents a significant therapeutic avenue.

Purpose of the Study:

• To review recent advancements in methyltransferase crystallographic structure resolution.
• To summarize the screening and development of bioactive inhibitors targeting DNMTs and HMTs.
• To elucidate the structure-function relationships and interaction mechanisms between methyltransferases and their inhibitors.

Main Methods:

• Review of published literature on methyltransferase structures.
• Analysis of crystallographic data for DNA and histone methyltransferases.
• Survey of identified bioactive inhibitors and their screening methodologies.

Main Results:

• Detailed discussion of DNA and HMT structural features.
• Elucidation of the mechanisms underlying methyltransferase inhibition.
• Exploration of structure-activity relationships for transferase inhibitors.

Conclusions:

• Methyltransferase inhibitors represent a promising class of therapeutic agents for various diseases.
• Understanding methyltransferase structure is crucial for rational drug design.
• Further research into inhibitor development holds significant potential for clinical applications.