S-adenosylmethionine synthetase enzyme
|PDB structures||RCSB PDB PDBe PDBsum|
In molecular biology, the protein S-adenosylmethionine synthetase (EC 22.214.171.124) also known as methionine adenosyltransferase (MAT), refers to an enzyme that catalyses the formation of S-adenosylmethionine (AdoMet) by joining methionine (a non-polar amino acid) and ATP (the basic currency of energy).
AdoMet is an important methyl donor for transmethylation, it gives away its methyl group and is also the propylamino donor in polyamine biosynthesis.S-adenosylmethionine synthetase can be considered rate-limiting step of the methionine cycle. S-adenosylmethionine is a methyl donor and allows DNA methylation. Once DNA is methylated it switches the genes off and therefore, S-adenosylmethionine can be considered to control gene expression. Therefore, since it turns genes on and off, it is clearly important. Furthermore, it is also involved in gene transcription, cell proliferation,and production of secondary metabolites. Hence it is fast becoming a drug target, in particular for the following diseases: depression, dementia, vacuolar myelopathy, liverinjury, migraine, osteoarthritis, and as a potential cancer chemopreventive agent. The importance of this enzyme is further characterised by it catalysing one of the most abundant processes in the cell. They require divalent cations namely Magnesium, Mg2+ for catalysis and are activated by monovalent ions such as potassium, K+. This article discusses the protein domains that make up the S-adenosylmethionine synthetase protein and how these domains contribute to its function of methylating genes. More specifically, this article explores the structure and function of the three protein domains found in this enzyme and the pseudo-3-fold symmetry that makes them well adapted to their function.Interestingly, all three domains of have the strikingly similar protein folding.
Conserved motifs in the 3'UTR of MAT2A mRNA 
A computational comparative analysis of vertebrate genome sequences have identified a cluster of 6 conserved hairpin motifs in the 3'UTR of the MAT2A messenger RNA (mRNA) transcript. The predicted hairpins (named A-F) have strong evolutionary conservation and 3 of the predicted RNA structures (hairpins A, C and D) have been confirmed by in-line probing analysis. No structural changes were observed for any of the hairpins in the presence of metabolites SAM, S-adenosylhomocysteine or L-Methioninine. They are proposed to be involved in transcript stability and their functionality is currently under investigation.
Protein overview 
The S-adenosylmethionine synthetase enzyme is found in almost every organism bar parasites which obtain AdoMet from their host. Isoenzymes are found in bacteria, budding yeast and even in mammalian mitochondria. Most MATs are homo-oligomers and the majority are tetramers. The monomers are organised into three domains formed by nonconsecutive stretches of the sequence, and the subunits interact through a large flat hydrophobic surface to form the dimers.
S-adenosylmethionine synthetase N terminal domain 
|S-adenosylmethionine synthetase N terminal domain|
S-adenosylmethionine synthetase with ADP
N terminal domain function 
The N terminal domain is well conserved across different species. This may be due to its important function in substrate and cation binding. The residues involved in methionine binding are found in the N-terminal domain.
N terminal domain structure 
S-adenosylmethionine synthetase Central domain 
|S-adenosylmethionine synthetase Central domain|
S-adenosylmethionine synthetase with ADP
Central terminal domain function 
The precise function of the central domain has not been fully elucidated, but it is thought to be important in aiding catalysis.
Central domain Structure 
S-adenosylmethionine synthetase, C terminal domain 
|S-adenosylmethionine synthetase, C-terminal domain|
Methionine adenosyltransferase in a complex ADP and l-methionine.
C terminal domain function 
The function of the C-terminal domain has been experimentally determined as being important for cytoplasmic localisation. The residues are scattered along the C-terminal domain sequence however once the protein folds, they position themselves closely together.
C terminal domain Structure 
The C-terminal domains contains two alpha-helices and four beta-strands.
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- Methionine adenosyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)
- EC 126.96.36.199