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Transferase PDB id
1mxc
Jmol
Contents
Protein chain
378 a.a. *
Ligands
PO4
ABP
Metals
_MG ×2
__K ×2
* Residue conservation analysis
PDB id:
1mxc
Name: Transferase
Title: S-adenosylmethionine synthetase with 8-br-adp
Structure: S-adenosylmethionine synthetase. Chain: a. Synonym: mat, atp\:l-methionine s-adenosyltransferase. Ec: 2.5.1.6
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Dimer (from PDB file)
Resolution:
3.00Å     R-factor:   0.187     R-free:   0.259
Authors: F.Takusagawa,S.Kamitori,G.D.Markham
Key ref:
F.Takusagawa et al. (1996). Structure and function of S-adenosylmethionine synthetase: crystal structures of S-adenosylmethionine synthetase with ADP, BrADP, and PPi at 28 angstroms resolution. Biochemistry, 35, 2586-2596. PubMed id: 8611562 DOI: 10.1021/bi952604z
Date:
10-Jan-96     Release date:   11-Jul-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0A817  (METK_ECOLI) -  S-adenosylmethionine synthase
Seq:
Struc: 		384 a.a.
378 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.5.1.6  - Methionine adenosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Methionine Adenosyltransferase
      Reaction: ATP + L-methionine + H2O = phosphate + diphosphate + S-adenosyl-L- methionine
ATP
Bound ligand (Het Group name = ABP)
matches with 84.38% similarity 		+ L-methionine
 + H(2)O
 =
phosphate
Bound ligand (Het Group name = PO4)
corresponds exactly 		+ diphosphate
 + S-adenosyl-L- methionine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     one-carbon metabolic process   2 terms 
  Biochemical function     nucleotide binding     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi952604z Biochemistry 35:2586-2596 (1996)
PubMed id: 8611562  
 
 
Structure and function of S-adenosylmethionine synthetase: crystal structures of S-adenosylmethionine synthetase with ADP, BrADP, and PPi at 28 angstroms resolution.
F.Takusagawa, S.Kamitori, G.D.Markham.
 
  ABSTRACT  
 
S-Adenosylmethionine synthetase (MAT,ATP:L-methionine S-adenosltransferase, EC 2.5.1.6) plays a central metabolic role in all organisms. MAT catalyzes the two-step reaction which synthesizes S-adenosylmethionine (AdoMet), pyrophosphate (PPi), and orthophosphate (Pi) from ATP and L-methionine. AdoMet is the primary methyl group donor in biological systems. The first crystal structure of MAT from Escherichia coli has recently been determined [Takusagawa et al. (1995) J. Biol. Chem. 271, 136-147]. In order to elucidate the active site and possible catalytic reaction mechanism, the MAT structures in the crystals grown with the substrate ATP (and BrATP) and the product PPi have been determined (space group P6(2)22; unit cell a = b = 128.9 Angstroms, c= 139.8 Angstroms, resolution limit 2.8 Angstroms; R O.19; Rfree 0.26). The enzyme consists of four identical subunits; two subunits form a spherical dimer, and pairs of these tightly bound dimers form a tetrameric enzyme. Each dimer has two active sites which are located between the subunits. Each subunit consists of three domains related to each other by a pseudo 3-fold symmetry. The crystal structures showed that the ATP molecules were hydrolyzed to ADP and Pi by the enzyme. Those products were found at the active site along with the essential metal ions (K+ and Mg2+). This rather unexpected finding was first confirmed by the structure of the complex with PPi and later by an HPLC analysis. The enzyme hydrolyzed ATP to ADP and Pi in 72 h under the same conditions as the crystallization of the enzyme. In the active site, the diphosphate moiety of ADP and Pi interacts extensively with amino acid residues from the two subunits of the enzyme, whereas the adenine and ribose moieties have little interaction with the enzyme. The enzyme structure is little changed upon binding ADP. All amino acid residues involved in the active site are found to be conserved in the 14 reported sequences of MAT from a wide range of organisms. Thus the structure determined in this study can be utilized as a model for other members of the MAT family. On the basis of the crystal structures, the catalytic reaction mechanisms of AdoMet formation and hydrolysis of tripolyphosphate are proposed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20038586 M.Sabaty, G.Adryanczyk, C.Roustan, S.Cuiné, C.Lamouroux, and D.Pignol (2010).
Coproporphyrin excretion and low thiol levels caused by point mutation in the Rhodobacter sphaeroides S-adenosylmethionine synthetase gene.
  J Bacteriol, 192, 1238-1248.  
19077162 A.L.Mallam (2009).
How does a knotted protein fold?
  FEBS J, 276, 365-375.  
19699176 G.D.Markham, F.Takusagawa, A.M.Dijulio, and C.W.Bock (2009).
An investigation of the catalytic mechanism of S-adenosylmethionine synthetase by QM/MM calculations.
  Arch Biochem Biophys, 492, 82-92.  
18953685 G.D.Markham, and M.A.Pajares (2009).
Structure-function relationships in methionine adenosyltransferases.
  Cell Mol Life Sci, 66, 636-648.  
19739644 J.C.Taylor, C.W.Bock, F.Takusagawa, and G.D.Markham (2009).
Discovery of novel types of inhibitors of S-adenosylmethionine synthesis by virtual screening.
  J Med Chem, 52, 5967-5973.  
17915037 P.Ho, K.F.Kong, Y.H.Chan, J.S.Tsang, and J.T.Wong (2007).
An unusual S-adenosylmethionine synthetase gene from dinoflagellate is methylated.
  BMC Mol Biol, 8, 87.  
17226041 P.R.Jesudhasan, and P.T.Woo (2007).
A S-adenosylmethionine synthetase gene from the pathogenic piscine hemoflagellate, Cryptobia salmositica.
  Parasitol Res, 100, 1401-1406.  
16365035 C.Lindermayr, G.Saalbach, G.Bahnweg, and J.Durner (2006).
Differential inhibition of Arabidopsis methionine adenosyltransferases by protein S-nitrosylation.
  J Biol Chem, 281, 4285-4291.  
15537083 K.W.Jeon (2004).
Genetic and physiological interactions in the amoeba-bacteria symbiosis.
  J Eukaryot Microbiol, 51, 502-508.  
15206944 Y.Pérez-Pertejo, R.M.Reguera, C.García-Estrada, R.Balaña-Fouce, and D.Ordóñez (2004).
Mutational analysis of methionine adenosyltransferase from Leishmania donovani.
  Eur J Biochem, 271, 2791-2798.  
12919315 R.K.Gordon, K.Ginalski, W.R.Rudnicki, L.Rychlewski, M.C.Pankaskie, J.M.Bujnicki, and P.K.Chiang (2003).
Anti-HIV-1 activity of 3-deaza-adenosine analogs. Inhibition of S-adenosylhomocysteine hydrolase and nucleotide congeners.
  Eur J Biochem, 270, 3507-3517.  
14612565 S.Prasad, K.J.Wright, D.Banerjee Roy, L.A.Bush, A.M.Cantwell, and E.Di Cera (2003).
Redesigning the monovalent cation specificity of an enzyme.
  Proc Natl Acad Sci U S A, 100, 13785-13790.  
11815619 M.M.Sánchez del Pino, I.Pérez-Mato, J.M.Sanz, J.M.Mato, and F.J.Corrales (2002).
Folding of dimeric methionine adenosyltransferase III: identification of two folding intermediates.
  J Biol Chem, 277, 12061-12066.  
11698393 R.M.Reguera, R.Balaña-Fouce, Y.Pérez-Pertejo, F.J.Fernández, C.García-Estrada, J.C.Cubría, C.Ordóñez, and D.Ordóñez (2002).
Cloning expression and characterization of methionine adenosyltransferase in Leishmania infantum promastigotes.
  J Biol Chem, 277, 3158-3167.  
10660564 J.C.Taylor, and G.D.Markham (2000).
The bifunctional active site of S-adenosylmethionine synthetase. Roles of the basic residues.
  J Biol Chem, 275, 4060-4065.  
  10674710 J.Y.Chou (2000).
Molecular genetics of hepatic methionine adenosyltransferase deficiency.
  Pharmacol Ther, 85, 1-9.  
10757994 M.S.McQueney, K.S.Anderson, and G.D.Markham (2000).
Energetics of S-adenosylmethionine synthetase catalysis.
  Biochemistry, 39, 4443-4454.  
10029549 C.Schalk-Hihi, and G.D.Markham (1999).
The conformations of a substrate and a product bound to the active site of S-adenosylmethionine synthetase.
  Biochemistry, 38, 2542-2550.  
10358060 I.Pérez-Mato, C.Castro, F.A.Ruiz, F.J.Corrales, and J.M.Mato (1999).
Methionine adenosyltransferase S-nitrosylation is regulated by the basic and acidic amino acids surrounding the target thiol.
  J Biol Chem, 274, 17075-17079.  
10551856 J.C.Taylor, and G.D.Markham (1999).
The bifunctional active site of s-adenosylmethionine synthetase. Roles of the active site aspartates.
  J Biol Chem, 274, 32909-32914.  
10413480 R.S.Reczkowski, and G.D.Markham (1999).
Slow binding inhibition of S-adenosylmethionine synthetase by imidophosphate analogues of an intermediate and product.
  Biochemistry, 38, 9063-9068.  
10387078 Y.Hu, J.Komoto, Y.Huang, T.Gomi, H.Ogawa, Y.Takata, M.Fujioka, and F.Takusagawa (1999).
Crystal structure of S-adenosylhomocysteine hydrolase from rat liver.
  Biochemistry, 38, 8323-8333.
PDB code: 1b3r
  9699005 M.A.Avila, F.J.Corrales, F.Ruiz, E.Sánchez-Góngora, J.Mingorance, M.V.Carretero, and I.M.Mato (1998).
Specific interaction of methionine adenosyltransferase with free radicals.
  Biofactors, 8, 27-32.  
9753435 R.S.Reczkowski, J.C.Taylor, and G.D.Markham (1998).
The active-site arginine of S-adenosylmethionine synthetase orients the reaction intermediate.
  Biochemistry, 37, 13499-13506.  
  9409150 D.Thomas, and Y.Surdin-Kerjan (1997).
Metabolism of sulfur amino acids in Saccharomyces cerevisiae.
  Microbiol Mol Biol Rev, 61, 503-532.  
  9042912 M.E.Chamberlin, T.Ubagai, S.H.Mudd, H.L.Levy, and J.Y.Chou (1997).
Dominant inheritance of isolated hypermethioninemia is associated with a mutation in the human methionine adenosyltransferase 1A gene.
  Am J Hum Genet, 60, 540-546.  
9461287 T.Hiroki, S.Horikawa, and K.Tsukada (1997).
Structure of the rat methionine adenosyltransferase 2A gene and its promoter.
  Eur J Biochem, 250, 653-660.  
  8939751 M.M.Dixon, S.Huang, R.G.Matthews, and M.Ludwig (1996).
The structure of the C-terminal domain of methionine synthase: presenting S-adenosylmethionine for reductive methylation of B12.
  Structure, 4, 1263-1275.
PDB code: 1msk
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.