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Updated: Apr 26, 2026
17:12
Profiling of Methyltransferases and Other S-adenosyl-L-homocysteine-binding Proteins by Capture Compound Mass Spectrometry CCMS
Published on: December 20, 2010
17.5K
Structure and function study of the complex that synthesizes S-adenosylmethionine.
Ben Murray1, Svetlana V Antonyuk2, Alberto Marina3
1Molecular Biophysics Group, Institute of Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, L69 7ZX, England ; Structural Biology Unit CIC bioGUNE, Parque Tecnológico de Bizkaia, 48160 Derio, Bizkaia, Spain.
Iucrj
|July 31, 2014
Summary
This study reveals the first structures of the S-Adenosylmethionine (SAMe) MATα2β complex, crucial for cell proliferation in cancers. The findings uncover its unique structure and regulation, offering new avenues for anticancer drug design.
Area of Science:
- Biochemistry
- Structural Biology
- Cancer Biology
Background:
- S-Adenosylmethionine (SAMe) is vital for cellular methylation and linked to liver and colon cancer proliferation.
- Methionine adenosyltransferase (MAT) enzymes, including MATα2 and MATβ subunits, synthesize SAMe.
- The MATα2β complex's structure and function have remained largely unknown despite its importance.
Purpose of the Study:
- To elucidate the first structures of the functional MATα2β complex.
- To understand the stoichiometry and regulatory mechanisms of the MATα2β complex.
- To explore the complex's role in hepatocellular carcinoma and its potential as a drug target.
Main Methods:
- X-ray crystallography
- Solution X-ray scattering
- Biochemical assays to determine enzyme kinetics.
Main Results:
- The first structures of the 258 kDa MATα2β complex were determined in both crystalline and solution states.
- An unexpected stoichiometry of 4 MATα2 subunits and 2 MATβV2 subunits was observed.
- Complex formation occurs via the C-terminal of MATβV2, with the N-terminal regulating activity, and the complex exhibits a 3-4 fold higher Vmax than MATα2 alone.
Conclusions:
- The study provides unprecedented structural insights into the MATα2β complex, revealing its unique assembly and regulatory mechanisms.
- The findings highlight the MATα2β complex's critical role in liver cancer and its potential as a target for novel anticancer therapies.
- This structural information opens pathways for structure-based drug design to target cancer-related SAMe metabolism.
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