PDBsum entry 1fug

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protein Protein-protein interface(s) links
Transferase PDB id
Protein chains
383 a.a. *
* Residue conservation analysis
PDB id:
Name: Transferase
Title: S-adenosylmethionine synthetase
Structure: S-adenosylmethionine synthetase. Chain: a, b. Synonym: mat, atp\:l-methionine s-adenosyltransferase. Engineered: yes. Other_details: tetragonal modification
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Tetramer (from PDB file)
3.20Å     R-factor:   0.210     R-free:   0.290
Authors: Z.Fu,G.D.Markham,F.Takusagawa
Key ref: Z.Fu et al. (1996). Flexible loop in the structure of S-adenosylmethionine synthetase crystallized in the tetragonal modification. J Biomol Struct Dyn, 13, 727-739. PubMed id: 8723769 DOI: 10.1080/07391102.1996.10508887
25-Feb-96     Release date:   01-Aug-96    
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Protein chains
Pfam   ArchSchema ?
P0A817  (METK_ECOLI) -  S-adenosylmethionine synthase
384 a.a.
383 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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

Methionine Adenosyltransferase
      Reaction: ATP + L-methionine + H2O = phosphate + diphosphate + S-adenosyl-L- methionine
+ L-methionine
+ H(2)O
= phosphate
+ 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     9 terms  


DOI no: 10.1080/07391102.1996.10508887 J Biomol Struct Dyn 13:727-739 (1996)
PubMed id: 8723769  
Flexible loop in the structure of S-adenosylmethionine synthetase crystallized in the tetragonal modification.
Z.Fu, Y.Hu, G.D.Markham, F.Takusagawa.
S-Adenosylmethionine synthetase (MAT, ATP:L-methionine S-adenosyltransferase, E.C. 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. MAT from Escherichia coli was crystallized in the tetragonal modification with space group P4(3)2(1)2 using the same conditions as previously yielded crystals of the hexagonal system [Takusagawa, et al., (1996), J. Biol. Chem. 171, 136-147], except for the crystallization temperature. The structure has been determined by molecular replacement at 3.2 A resolution. The overall structure of the tetrameric MAT in the tetragonal modification is essentially the same as the structure found in the hexagonal modification. However there are two remarkable differences between the structures of two modifications. One is the contents in the active sites (holoform vs. apo-form), and the other is the conformation of the flexible loop over the active site (open vs. closed). These differences in the crystal structures are caused solely by the difference in crystallization temperatures (26 degrees C vs. 4 degrees C). We have interpreted the structural data obtained from the X-ray analyses in conjunction with the results of the mechanistic and sequencing studies in terms of possible dynamic motion of the flexible loop. When a substrate/product binds in the active site (hexagonal modification), the loop becomes disordered, apparently due to flexibility at the entrance of the active site as if it acts as a "mobile loop" during the catalytic reaction. On the other hand, when the temperature is decreased, the dynamic motion of the flexible loop may be reduced, and the loop residues enter the active site and close its entrance (tetragonal modification). Thus, the active site of the tetragonal modification is empty despite the crystals being grown in mother liquor containing a large concentration of phosphate (100 mM). There is no significant displacement of amino acid residues in the active site between the holo and apo forms, suggesting that the flexible loop plays an important role in determination of the contents in the active site. Since the functionally important amino acid residues in the active site are all conserved throughout various species, the structures of the active sites and the mechanism of the catalysis are probably essentially identical in the enzymes from a wide range of organisms. However, the substrate KM and Vmax values of MATs from various species are distributed over a wide range. The amino acid residues in the flexible loop regions are poorly conserved throughout various species. Therefore, the wide differences in catalysis rates of MATs from various speeches may be due to the differences in the composition of the flexible loop.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
16978047 P.Virnau, L.A.Mirny, and M.Kardar (2006).
Intricate knots in proteins: Function and evolution.
  PLoS Comput Biol, 2, e122.  
15898109 J.Parsons, J.B.Holmes, J.M.Rojas, J.Tsai, and C.E.Strauss (2005).
Practical conversion from torsion space to Cartesian space for in silico protein synthesis.
  J Comput Chem, 26, 1063-1068.  
11741996 Z.Hou, W.Wang, H.J.Fromm, and R.B.Honzatko (2002).
IMP Alone Organizes the Active Site of Adenylosuccinate Synthetase from Escherichia coli.
  J Biol Chem, 277, 5970-5976.
PDB codes: 1kjx 1kkb 1kkf
10629195 F.J.Ruzicka, K.W.Lieder, and P.A.Frey (2000).
Lysine 2,3-aminomutase from Clostridium subterminale SB4: mass spectral characterization of cyanogen bromide-treated peptides and cloning, sequencing, and expression of the gene kamA in Escherichia coli.
  J Bacteriol, 182, 469-476.  
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.  
10757994 M.S.McQueney, K.S.Anderson, and G.D.Markham (2000).
Energetics of S-adenosylmethionine synthetase catalysis.
  Biochemistry, 39, 4443-4454.  
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.  
9708979 J.Y.Choe, B.W.Poland, H.J.Fromm, and R.B.Honzatko (1998).
Role of a dynamic loop in cation activation and allosteric regulation of recombinant porcine fructose-1,6-bisphosphatase.
  Biochemistry, 37, 11441-11450.
PDB codes: 1bfl 1cnq
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.  
9346283 G.Lange-Savage, H.Berchtold, A.Liesum, K.H.Budt, A.Peyman, J.Knolle, J.Sedlacek, M.Fabry, and R.Hilgenfeld (1997).
Structure of HOE/BAY 793 complexed to human immunodeficiency virus (HIV-1) protease in two different crystal forms--structure/function relationship and influence of crystal packing.
  Eur J Biochem, 248, 313-322.
PDB codes: 1vij 1vik
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