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PDBsum entry 1u1h

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protein ligands metals links
Transferase PDB id
1u1h
Jmol
Contents
Protein chain
746 a.a. *
Ligands
SO4 ×4
MET
Metals
_ZN ×2
Waters ×286
* Residue conservation analysis
PDB id:
1u1h
Name: Transferase
Title: A. Thaliana cobalamine independent methionine synthase
Structure: 5-methyltetrahydropteroyltriglutamate-- homocysteine methyltransferase. Chain: a. Synonym: vitamin-b12-independent methionine synthase isozyme, cobalamin-independent methionine synthase isozyme. Engineered: yes
Source: Arabidopsis thaliana. Thale cress. Organism_taxid: 3702. Gene: cims. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.55Å     R-factor:   0.214     R-free:   0.260
Authors: J.-L.Ferrer,S.Ravanel,M.Robert,R.Dumas
Key ref:
J.L.Ferrer et al. (2004). Crystal structures of cobalamin-independent methionine synthase complexed with zinc, homocysteine, and methyltetrahydrofolate. J Biol Chem, 279, 44235-44238. PubMed id: 15326182 DOI: 10.1074/jbc.C400325200
Date:
15-Jul-04     Release date:   02-Sep-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O50008  (METE_ARATH) -  5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase 1
Seq:
Struc:
 
Seq:
Struc:
765 a.a.
746 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.1.1.14  - 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = tetrahydropteroyltri-L-glutamate + L-methionine
5-methyltetrahydropteroyltri-L-glutamate
+ L-homocysteine
= tetrahydropteroyltri-L-glutamate
+
L-methionine
Bound ligand (Het Group name = MET)
corresponds exactly
      Cofactor: Zinc
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     apoplast   12 terms 
  Biological process     microtubule cytoskeleton organization   7 terms 
  Biochemical function     transferase activity     7 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.C400325200 J Biol Chem 279:44235-44238 (2004)
PubMed id: 15326182  
 
 
Crystal structures of cobalamin-independent methionine synthase complexed with zinc, homocysteine, and methyltetrahydrofolate.
J.L.Ferrer, S.Ravanel, M.Robert, R.Dumas.
 
  ABSTRACT  
 
Cobalamin-independent methionine synthase (MetE) catalyzes the synthesis of methionine by a direct transfer of the methyl group of N5-methyltetrahydrofolate (CH3-H2PteGlun) to the sulfur atom of homocysteine (Hcy). We report here the first crystal structure of this metalloenzyme under different forms, free or complexed with the Hcy and folate substrates. The Arabidopsis thaliana MetE (AtMetE) crystals reveal a monomeric structure built by two (betaalpha)8 barrels making a deep groove at their interface. The active site is located at the surface of the C-terminal domain, facing the large interdomain cleft. Inside the active site, His647, Cys649, and Cys733 are involved in zinc coordination, whereas Asp605, Ile437, and Ser439 interact with Hcy. Opposite the zinc/Hcy binding site, a cationic loop (residues 507-529) belonging to the C-terminal domain anchors the first glutamyl residue of CH3-H4PteGlu5. The pterin moiety of CH3-H4PteGlu5 is stacked with Trp567, enabling the N5-methyl group to protrude in the direction of the zinc atom. These data suggest a structural role of the N-terminal domain of AtMetE in the stabilization of loop 507-529 and in the interaction with the poly-glutamate chain of CH3-H4PteGlun. Comparison of AtMetE structures reveals that the addition of Hcy does not lead to a direct coordination of the sulfur atom with zinc but to a reorganization of the zinc binding site with a stronger coordination to Cys649, Cys733, and a water molecule.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. Structure of the Arabidopsis MetE. a, ribbon diagram of AtMetE in complex with Met and PteGlu[5]. The Met and PteGlu[5] molecules are depicted as sticks and balls. The N-terminal domain is gold, the C-terminal domain is blue, and the zinc atom is green. b, structural alignment with the Hcy domain of MetH (in pink, code 1Q8A in the Protein Data Bank) performed with DALI. Secondary structures are shown only for residues 416-792 for AtMetE. Diagrams were produced with MOLSCRIPT (22) and rendered with POV-RAY (www.povray.org).
Figure 3.
FIG. 3. Charge colored surface of the methyl donor binding site. This figure, showing AtMetE complexed with CH[3]-H[4]PteGlu[5] and Met, was produced with DINO (Visualizing Structural Biology, 2002, www.dino3d.org).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 44235-44238) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20238167 M.A.Assarehzadegan, M.Sankian, F.Jabbari, M.Tehrani, R.Falak, and A.Varasteh (2011).
Identification of methionine synthase (Sal k 3), as a novel allergen of Salsola kali pollen.
  Mol Biol Rep, 38, 65-73.  
  20582239 T.Petrossian, and S.Clarke (2009).
Bioinformatic Identification of Novel Methyltransferases.
  Epigenomics, 1, 163-175.  
18772284 A.M.Krishnakumar, D.Sliwa, J.A.Endrizzi, E.S.Boyd, S.A.Ensign, and J.W.Peters (2008).
Getting a handle on the role of coenzyme M in alkene metabolism.
  Microbiol Mol Biol Rev, 72, 445-456.  
18296644 M.Koutmos, R.Pejchal, T.M.Bomer, R.G.Matthews, J.L.Smith, and M.L.Ludwig (2008).
Metal active site elasticity linked to activation of homocysteine in methionine synthases.
  Proc Natl Acad Sci U S A, 105, 3286-3291.
PDB codes: 3bof 3bol 3bq5 3bq6
17935688 H.S.Suliman, D.R.Appling, and J.D.Robertus (2007).
The gene for cobalamin-independent methionine synthase is essential in Candida albicans: a potential antifungal target.
  Arch Biochem Biophys, 467, 218-226.  
17376731 J.Penner-Hahn (2007).
Zinc-promoted alkyl transfer: a new role for zinc.
  Curr Opin Chem Biol, 11, 166-171.  
16525757 R.A.Azevedo, M.Lancien, and P.J.Lea (2006).
The aspartic acid metabolic pathway, an exciting and essential pathway in plants.
  Amino Acids, 30, 143-162.  
16618098 R.E.Taurog, and R.G.Matthews (2006).
Activation of methyltetrahydrofolate by cobalamin-independent methionine synthase.
  Biochemistry, 45, 5092-5102.  
  17012790 T.M.Fu, X.Y.Zhang, L.F.Li, Y.H.Liang, and X.D.Su (2006).
Preparation, crystallization and preliminary X-ray analysis of the methionine synthase (MetE) from Streptococcus mutans.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 984-985.  
15944751 L.Huang, D.Y.Li, S.X.Wang, S.M.Zhang, J.H.Chen, and X.F.Wu (2005).
Cloning and identification of methionine synthase gene from Pichia pastoris.
  Acta Biochim Biophys Sin (Shanghai), 37, 371-378.  
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 codes are shown on the right.