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| {{Infobox enzyme
| | I'm a 31 years old and work at the university (Economics).<br>In my spare time I try to teach myself Bengali. I have been there and look forward to go there sometime in the future. I like to read, preferably on my beloved Kindle. I like to watch CSI and The Big Bang Theory as well as docus about nature. I love Travel. |
| | Name = Methionine adenosyltransferase
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| | EC_number = 2.5.1.6
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| | CAS_number = 9012-52-6
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| | IUBMB_EC_number = 2/5/1/6
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| | GO_code =
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| In [[molecular biology]], the [[protein]] '''S-adenosylmethionine synthetase''' ({{EC number|2.5.1.6}}) also known as methionine adenosyltransferase (MAT), refers to an [[enzyme]] that [[Catalysis|catalyses]] the formation of [[S-Adenosyl methionine|S-adenosylmethionine]] (AdoMet) by joining [[methionine]] (a [[non-polar]] [[amino acid]]) and [[Adenosine triphosphate|ATP]] (the basic currency of energy).<ref name="pmid1696256">{{cite journal | author = Horikawa S, Sasuga J, Shimizu K, Ozasa H, Tsukada K | title = Molecular cloning and nucleotide sequence of cDNA encoding the rat kidney S-adenosylmethionine synthetase | journal = J. Biol. Chem. | volume = 265 | issue = 23 | pages = 13683–6 |date=August 1990 | pmid = 1696256 | doi = | url = }}</ref>
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| == Function ==
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| AdoMet is a [[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 the rate-limiting step of the methionine cycle.<ref name="pmid18953685">{{cite journal| author=Markham GD, Pajares MA| title=Structure-function relationships in methionine adenosyltransferases. | journal=Cell Mol Life Sci | year= 2009 | volume= 66 | issue= 4 | pages= 636–48 | pmid=18953685 | doi=10.1007/s00018-008-8516-1 | pmc=2643306 }}</ref>
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| S-adenosylmethionine (SAM) 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]].<ref name="pmid19497982">{{cite journal| author=Reytor E, Pérez-Miguelsanz J, Alvarez L, Pérez-Sala D, Pajares MA| title=Conformational signals in the C-terminal domain of methionine adenosyltransferase I/III determine its nucleocytoplasmic distribution. | journal=FASEB J | year= 2009 | volume= 23 | issue= 10 | pages= 3347–60 | pmid=19497982 | doi=10.1096/fj.09-130187 }}</ref>
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| SAM is also involved in [[transcription (genetics)|gene transcription]], [[cell proliferation]], and production of secondary metabolites.<ref name="pmid21989639">{{cite journal| author=Yoon S, Lee W, Kim M, Kim TD, Ryu Y| title=Structural and functional characterization of S-adenosylmethionine (SAM) synthetase from Pichia ciferrii. | journal=Bioprocess Biosyst Eng | year= 2012 | volume= 35 | issue= 1-2 | pages= 173–81 | pmid=21989639 | doi=10.1007/s00449-011-0640-x }}</ref> Hence it is fast becoming a drug target, in particular for the following diseases: [[depression (mood)|depression]], [[dementia]], vacuolar myelopathy, [[liver]] injury, [[migraine]], [[osteoarthritis]], and as a potential [[cancer]] chemopreventive agent.<ref name="pmid18634909">{{cite journal| author=Kamarthapu V, Rao KV, Srinivas PN, Reddy GB, Reddy VD| title=Structural and kinetic properties of Bacillus subtilis S-adenosylmethionine synthetase expressed in Escherichia coli. | journal=Biochim Biophys Acta | year= 2008 | volume= 1784 | issue= 12 | pages= 1949–58 | pmid=18634909 | doi=10.1016/j.bbapap.2008.06.006 }}</ref>
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| 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.<ref name="pmid8550549">{{cite journal| author=Takusagawa F, Kamitori S, Misaki S, Markham GD| title=Crystal structure of S-adenosylmethionine synthetase. | journal=J Biol Chem | year= 1996 | volume= 271 | issue= 1 | pages= 136–47 | pmid=8550549 | doi= }}</ref>
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| This enzyme [[catalysis|catalyses]] the following [[chemical reaction]]
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| : ATP + L-[[methionine]] + H<sub>2</sub>O <math>\rightleftharpoons</math> [[phosphate]] + [[diphosphate]] + [[S-adenosyl-L-methionine]]
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| ==Conserved motifs in the 3'UTR of MAT2A mRNA ==
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| A computational comparative analysis of vertebrate [[genome sequence]]s have identified a cluster of 6 conserved [[stem-loop|hairpin]] motifs in the [[3'UTR]] of the MAT2A [[MRNA|messenger RNA]] (mRNA) transcript.<ref name="pmid21994249">{{cite journal | author = Parker BJ, Moltke I, Roth A, Washietl S, Wen J, Kellis M, Breaker R, Pedersen JS | title = New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes | journal = Genome Res. | volume = 21 | issue = 11 | pages = 1929–43 |date=November 2011 | pmid = 21994249 | pmc = 3205577 | doi = 10.1101/gr.112516.110 }}</ref> 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 [[Nucleic_acid_structure_determination#In-line_probing|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.<ref name=pmid21994249/>
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| ==Protein overview==
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| The S-adenosylmethionine synthetase enzyme is found in almost every organism bar parasites which obtain AdoMet from their host. [[Isoenzyme]]s are found in bacteria, [[Saccharomyces cerevisiae|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.<ref name="pmid21605677">{{cite journal| author=Garrido F, Estrela S, Alves C, Sánchez-Pérez GF, Sillero A, Pajares MA| title=Refolding and characterization of methionine adenosyltransferase from Euglena gracilis. | journal=Protein Expr Purif | year= 2011 | volume= 79 | issue= 1 | pages= 128–36 | pmid=21605677 | doi=10.1016/j.pep.2011.05.004 }}</ref>
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| ==S-adenosylmethionine synthetase N terminal domain==
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| {{Infobox protein family
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| | Symbol = S-AdoMet_synt_N
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| | Name = S-adenosylmethionine synthetase N terminal domain
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| | image = PDB 1mxb EBI.jpg
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| | width =
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| | caption = S-adenosylmethionine synthetase with ADP
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| | Pfam = PF00438
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| | Pfam_clan =
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| | InterPro = IPR022628
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| | SMART =
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| | PROSITE = PDOC00369
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| | MEROPS =
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| | SCOP = 1mxa
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| | TCDB =
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| | OPM family =
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| | OPM protein =
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| | CAZy =
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| | CDD =
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| }}
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| In [[molecular biology]] the [[protein domain]] '''S-adenosylmethionine synthetase N terminal domain''' is found at the [[N-terminal]] of the enzyme.
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| ===N terminal domain function===
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| The N terminal domain is well conserved across different species. This may be due to its important function in [[substrate (biochemistry)|substrate]] and [[cation]] binding. The [[amino acid|residues]] involved in methionine binding are found in the N-terminal domain.<ref name="pmid21605677"/> | |
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| ===N terminal domain structure===
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| The N terminal region contains two [[alpha helix|alpha helices]] and four [[beta strands]].<ref name="pmid8550549"/>
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| ==S-adenosylmethionine synthetase Central domain==
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| {{Infobox protein family
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| | Symbol = S-AdoMet_synt_M
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| | Name =S-adenosylmethionine synthetase Central domain
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| | image = PDB 1mxb EBI.jpg
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| | width =
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| | caption = S-adenosylmethionine synthetase with ADP
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| | Pfam = PF02772
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| | Pfam_clan =
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| | InterPro = IPR022629
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| | SMART =
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| | PROSITE = PDOC00369
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| | MEROPS =
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| | SCOP = 1mxa
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| | TCDB =
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| | OPM family =
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| | OPM protein =
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| | CAZy =
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| | CDD =
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| }}
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| ===Central terminal domain function===
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| The precise function of the central domain has not been fully elucidated, but it is thought to be important in aiding catalysis.
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| ===Central domain Structure===
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| The central region contains two [[alpha helix|alpha helices]] and four [[beta strands]].<ref name="pmid8550549"/>
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| ==S-adenosylmethionine synthetase, C terminal domain==
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| {{Infobox protein family
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| | Symbol = S-AdoMet_synt_C
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| | Name = S-adenosylmethionine synthetase, C-terminal domain
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| | image = PDB 1o92 EBI.jpg
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| | width =
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| | caption = Methionine adenosyltransferase in a complex ADP and l-methionine.
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| | Pfam = PF02773
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| | Pfam_clan =
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| | InterPro = IPR022630
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| | SMART =
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| | PROSITE = PDOC00369
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| | MEROPS =
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| | SCOP = 1mxa
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| | TCDB =
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| | OPM family =
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| | OPM protein =
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| | CAZy =
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| | CDD =
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| }}
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| In [[molecular biology]], the [[protein domain]] '''S-adenosylmethionine synthetase, C-terminal domain''' refers to the [[C terminus]] of the S-adenosylmethionine synthetase
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| ===C terminal domain function===
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| The function of the C-terminal domain has been experimentally determined as being important for cytoplasmic localisation. The [[amino acid|residues]] are scattered along the C-terminal domain sequence however once the protein folds, they position themselves closely together.<ref name="pmid19497982"/>
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| ===C terminal domain Structure===
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| The C-terminal domains contains two alpha-helices and four beta-strands.<ref name="pmid8550549"/>
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| ==References==
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| {{reflist}}
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| ==External links==
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| * {{MeshName|Methionine+adenosyltransferase}}
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| * {{EC number|2.5.1.6}}
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| {{Alkyl and aryl transferases}}
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| {{Amino acid metabolism enzymes}}
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| {{InterPro content|IPR022630}}
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| [[Category:Protein domains]]
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| [[Category:Enzymes]]
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| [[Category:Methylating agents]]
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| [[Category:Gene expression]]
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| [[Category:Protein families]]
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| [[Category:Transferases]]
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| [[Category:Metabolism]]
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| [[Category:EC 2.5.1]]
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I'm a 31 years old and work at the university (Economics).
In my spare time I try to teach myself Bengali. I have been there and look forward to go there sometime in the future. I like to read, preferably on my beloved Kindle. I like to watch CSI and The Big Bang Theory as well as docus about nature. I love Travel.