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114  structures 8313  species 0  interactions 11392  sequences 51  architectures

Family: S-AdoMet_synt_C (PF02773)

Summary: S-adenosylmethionine synthetase, C-terminal domain

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This is the Wikipedia entry entitled "S-adenosylmethionine synthetase enzyme". More...

S-adenosylmethionine synthetase enzyme Edit Wikipedia article

Methionine adenosyltransferase
S-adenosylmethionine synthase 2, tetramer, Human
EC number2.5.1.6
CAS number9012-52-6
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum

S-adenosylmethionine synthetase (EC (also known as methionine adenosyltransferase (MAT)) is an enzyme that creates S-adenosylmethionine (a.k.a. AdoMet, SAM or SAMe) by reacting methionine (a non-polar amino acid) and ATP (the basic currency of energy).[1]


AdoMet is a methyl donor for transmethylation. It gives away its methyl group and is also the propylamino donor in polyamine biosynthesis. S-adenosylmethionine synthesis can be considered the rate-limiting step of the methionine cycle.[2]

As a methyl donor SAM allows DNA methylation. Once DNA is methylated, it switches the genes off and therefore, S-adenosylmethionine can be considered to control gene expression.[3]

SAM is also involved in gene transcription, cell proliferation, and production of secondary metabolites.[4] Hence SAM synthetase is fast becoming a drug target, in particular for the following diseases: depression, dementia, vacuolar myelopathy, liver injury, migraine, osteoarthritis, and as a potential cancer chemopreventive agent.[5]

This article discusses the protein domains that make up the SAM synthetase enzyme and how these domains contribute to its function. More specifically, this article explores the shared pseudo-3-fold symmetry that makes the domains well-adapted to their functions.[6]

This enzyme catalyses the following chemical reaction

ATP + L-methionine + H2O phosphate + diphosphate + S-adenosyl-L-methionine

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.[7] 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.[7]

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.[8]

S-adenosylmethionine synthetase N terminal domain

S-adenosylmethionine synthetase N terminal domain
PDB 1mxb EBI.jpg
S-adenosylmethionine synthetase with ADP

In molecular biology the protein domain S-adenosylmethionine synthetase N terminal domain is found at the N-terminal of the enzyme.

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.[8]

N terminal domain structure

The N terminal region contains two alpha helices and four beta strands.[6]

S-adenosylmethionine synthetase Central domain

S-adenosylmethionine synthetase Central domain
PDB 1mxb EBI.jpg
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

The central region contains two alpha helices and four beta strands.[6]

S-adenosylmethionine synthetase, C terminal domain

S-adenosylmethionine synthetase, C-terminal domain
PDB 1o92 EBI.jpg
Methionine adenosyltransferase in a complex ADP and l-methionine.

In molecular biology, the protein domain S-adenosylmethionine synthetase, C-terminal domain refers to the C terminus of the S-adenosylmethionine synthetase

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.[3]

C terminal domain Structure

The C-terminal domains contains two alpha-helices and four beta-strands.[6]


  1. ^ Horikawa S, Sasuga J, Shimizu K, Ozasa H, Tsukada K (August 1990). "Molecular cloning and nucleotide sequence of cDNA encoding the rat kidney S-adenosylmethionine synthetase". J. Biol. Chem. 265 (23): 13683–6. PMID 1696256.
  2. ^ Markham GD, Pajares MA (2009). "Structure-function relationships in methionine adenosyltransferases". Cell Mol Life Sci. 66 (4): 636–48. doi:10.1007/s00018-008-8516-1. PMC 2643306. PMID 18953685.
  3. ^ a b Reytor E, Pérez-Miguelsanz J, Alvarez L, Pérez-Sala D, Pajares MA (2009). "Conformational signals in the C-terminal domain of methionine adenosyltransferase I/III determine its nucleocytoplasmic distribution". FASEB J. 23 (10): 3347–60. doi:10.1096/fj.09-130187. hdl:10261/55151. PMID 19497982.
  4. ^ Yoon S, Lee W, Kim M, Kim TD, Ryu Y (2012). "Structural and functional characterization of S-adenosylmethionine (SAM) synthetase from Pichia ciferrii". Bioprocess Biosyst Eng. 35 (1–2): 173–81. doi:10.1007/s00449-011-0640-x. PMID 21989639.
  5. ^ Kamarthapu V, Rao KV, Srinivas PN, Reddy GB, Reddy VD (2008). "Structural and kinetic properties of Bacillus subtilis S-adenosylmethionine synthetase expressed in Escherichia coli". Biochim Biophys Acta. 1784 (12): 1949–58. doi:10.1016/j.bbapap.2008.06.006. PMID 18634909.
  6. ^ a b c d Takusagawa F, Kamitori S, Misaki S, Markham GD (1996). "Crystal structure of S-adenosylmethionine synthetase". J Biol Chem. 271 (1): 136–47. doi:10.1074/jbc.271.1.136. PMID 8550549.
  7. ^ a b Parker BJ, Moltke I, Roth A, Washietl S, Wen J, Kellis M, Breaker R, Pedersen JS (November 2011). "New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes". Genome Res. 21 (11): 1929–43. doi:10.1101/gr.112516.110. PMC 3205577. PMID 21994249.
  8. ^ a b Garrido F, Estrela S, Alves C, Sánchez-Pérez GF, Sillero A, Pajares MA (2011). "Refolding and characterization of methionine adenosyltransferase from Euglena gracilis". Protein Expr Purif. 79 (1): 128–36. doi:10.1016/j.pep.2011.05.004. hdl:10261/55441. PMID 21605677.

External links

This article incorporates text from the public domain Pfam and InterPro: IPR022630

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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S-adenosylmethionine synthetase, C-terminal domain Provide feedback

The three domains of S-adenosylmethionine synthetase have the same alpha+beta fold.

Literature references

  1. Takusagawa F, Kamitori S, Markham GD; , Biochemistry 1996;35:2586-2596.: Structure and function of S-adenosylmethionine synthetase: crystal structures of S-adenosylmethionine synthetase with ADP, BrADP, and PPi at 28 angstroms resolution. PUBMED:8611562 EPMC:8611562

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR022630

S-adenosylmethionine synthetase (MAT, EC ) is the enzyme that catalyzes the formation of S-adenosylmethionine (AdoMet) from methionine and ATP [ PUBMED:1696256 ]. AdoMet is an important methyl donor for transmethylation and is also the propylamino donor in polyamine biosynthesis.

In bacteria there is a single isoform of AdoMet synthetase (gene metK), there are two in budding yeast (genes SAM1 and SAM2) and in mammals while in plants there is generally a multigene family.

The sequence of AdoMet synthetase is highly conserved throughout isozymes and species. The active sites of both the Escherichia coli and rat liver MAT reside between two subunits, with contributions from side chains of residues from both subunits, resulting in a dimer as the minimal catalytic entity. The side chains that contribute to the ligand binding sites are conserved between the two proteins. In the structures of complexes with the E. coli enzyme, the phosphate groups have the same positions in the (PPi plus Pi) complex and the (ADP plus Pi) complex and are located at the bottom of a deep cavity with the adenosyl group nearer the entrance [ PUBMED:1213535 ].

The three domains of S-adenosylmethionine synthetase have the same alpha+beta fold. This entry represents the C-terminal domain of S=adenosylmethionine synthetase and is found in association with and .

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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Seed source: Prosite
Previous IDs: S-AdoMet_syntD3;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Griffiths-Jones SR
Number in seed: 303
Number in full: 11392
Average length of the domain: 138.20 aa
Average identity of full alignment: 64 %
Average coverage of the sequence by the domain: 35.24 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 25.1 25.1
Noise cut-off 24.5 24.7
Model length: 138
Family (HMM) version: 18
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Species distribution

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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the S-AdoMet_synt_C domain has been found. There are 114 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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