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PDBsum entry 1khh

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1khh
Jmol
Contents
Protein chains
193 a.a. *
Ligands
SAH ×2
Waters ×162
* Residue conservation analysis
PDB id:
1khh
Name: Transferase
Title: Crystal structure of guanidinoacetate methyltransferase from rat liver: a template structure of protein arginine methyltransferase
Structure: Guanidinoacetate methyltransferase. Chain: a, b. Fragment: n-terminal truncation. Synonym: guanidinoacetate n-methyltransferase. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.214     R-free:   0.284
Authors: F.Takusagawa,J.Komoto
Key ref:
J.Komoto et al. (2002). Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase. J Mol Biol, 320, 223-235. PubMed id: 12079381 DOI: 10.1016/S0022-2836(02)00448-5
Date:
30-Nov-01     Release date:   12-Dec-01    
PROCHECK
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 Headers
 References

Protein chains
Pfam  
P10868  (GAMT_RAT) -  Guanidinoacetate N-methyltransferase
Seq:
Struc:
236 a.a.
193 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.1.1.2  - Guanidinoacetate N-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Creatine Biosynthesis
      Reaction: S-adenosyl-L-methionine + guanidinoacetate = S-adenosyl-L-homocysteine + creatine
S-adenosyl-L-methionine
+ guanidinoacetate
=
S-adenosyl-L-homocysteine
Bound ligand (Het Group name = SAH)
corresponds exactly
+ creatine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     guanidinoacetate N-methyltransferase activity     1 term  

 

 
    reference    
 
 
DOI no: 10.1016/S0022-2836(02)00448-5 J Mol Biol 320:223-235 (2002)
PubMed id: 12079381  
 
 
Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase.
J.Komoto, Y.Huang, Y.Takata, T.Yamada, K.Konishi, H.Ogawa, T.Gomi, M.Fujioka, F.Takusagawa.
 
  ABSTRACT  
 
Guanidinoacetate methyltransferase (GAMT) is the enzyme that catalyzes the last step of creatine biosynthesis. The enzyme is found in abundance in the livers of all vertebrates. Recombinant rat liver GAMT has been crystallized with S-adenosylhomocysteine (SAH), and the crystal structure has been determined at 2.5 A resolution. The 36 amino acid residues at the N terminus were cleaved during the purification and the truncated enzyme was crystallized. The truncated enzyme forms a dimer, and each subunit contains one SAH molecule in the active site. Arg220 of the partner subunit forms a pair of hydrogen bonds with Asp134 at the guanidinoacetate-binding site. On the basis of the crystal structure, site-directed mutagenesis on Asp134, and chemical modification and limited proteolysis studies, we propose a catalytic mechanism of this enzyme. The truncated GAMT dimer structure can be seen as a ternary complex of protein arginine methyltransferase (one subunit) complexed with a protein substrate (the partner subunit) and the product SAH. Therefore, this structure provides insight into the structure and catalysis of protein arginine methyltransferases.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Topology diagram. The small numbers in the rectangles and arrows represent amino acid residue numbers. The helices with broken lines are under the b-sheet.
Figure 10.
Figure 10. A superimposed active-site view of GAMT and PRMT3 showing the similar locations of the essential amino acid residues of the proposed catalytic reaction mechanism. The bound SAH of PRMT3 was superimposed on the bound SAH of GAMT by the least-squares method. The GAMT and PRMT3 are colored aquamarine and light pink, respectively. An arginine residue (Arg with white bonds) is placed in the active site of PRMT3 by superimposing the carboxylate group of Asp134 three dots, centered Arg220B section of GAMT on that of Glu326 of PRMT3. Possible polar interactions are indicated by thin lines.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 320, 223-235) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18221488 G.Brosch, P.Loidl, and S.Graessle (2008).
Histone modifications and chromatin dynamics: a focus on filamentous fungi.
  FEMS Microbiol Rev, 32, 409-439.  
17005254 C.D.Krause, Z.H.Yang, Y.S.Kim, J.H.Lee, J.R.Cook, and S.Pestka (2007).
Protein arginine methyltransferases: evolution and assessment of their pharmacological and therapeutic potential.
  Pharmacol Ther, 113, 50-87.  
15195996 A.Dong, L.Zhou, X.Zhang, S.Stickel, R.J.Roberts, and X.Cheng (2004).
Structure of the Q237W mutant of HhaI DNA methyltransferase: an insight into protein-protein interactions.
  Biol Chem, 385, 373-379.
PDB code: 1svu
15273252 A.Jansson, H.Koskiniemi, P.Mäntsälä, J.Niemi, and G.Schneider (2004).
Crystal structure of a ternary complex of DnrK, a methyltransferase in daunorubicin biosynthesis, with bound products.
  J Biol Chem, 279, 41149-41156.
PDB codes: 1tw2 1tw3
12925789 J.Komoto, Y.Takata, T.Yamada, K.Konishi, H.Ogawa, T.Gomi, M.Fujioka, and F.Takusagawa (2003).
Monoclinic guanidinoacetate methyltransferase and gadolinium ion-binding characteristics.
  Acta Crystallogr D Biol Crystallogr, 59, 1589-1596.
PDB codes: 1p1b 1p1c
12399454 T.Velkov, and A.Lawen (2003).
Mapping and molecular modeling of S-adenosyl-L-methionine binding sites in N-methyltransferase domains of the multifunctional polypeptide cyclosporin synthetase.
  J Biol Chem, 278, 1137-1148.  
12389038 S.A.Jacobs, J.M.Harp, S.Devarakonda, Y.Kim, F.Rastinejad, and S.Khorasanizadeh (2002).
The active site of the SET domain is constructed on a knot.
  Nat Struct Biol, 9, 833-838.
PDB codes: 1mt6 1muf
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.