PDBsum entry 1xr2

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Transferase PDB id
Protein chains
715 a.a. *
SO4 ×2
C2F ×2
MRY ×2
Waters ×238
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of oxidized t. Maritima cobalamin- independent methionine synthase complexed with methyltetrahydrofolate
Structure: 5-methyltetrahydropteroyltriglutamate-- homocysteine methyltransferase. Chain: a, b. Synonym: methionine synthase, vitamin-b12 independent isozyme, cobalamin-independent methionine synthase. Engineered: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Gene: mete. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.35Å     R-factor:   0.207     R-free:   0.254
Authors: R.Pejchal,M.L.Ludwig
Key ref: R.Pejchal and M.L.Ludwig (2005). Cobalamin-independent methionine synthase (MetE): a face-to-face double barrel that evolved by gene duplication. PLoS Biol, 3, e31-264. PubMed id: 15630480
13-Oct-04     Release date:   01-Mar-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q9X112  (METE_THEMA) -  5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase
734 a.a.
715 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.  - 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = tetrahydropteroyltri-L-glutamate + L-methionine
Bound ligand (Het Group name = C2F)
matches with 61.00% similarity
Bound ligand (Het Group name = MRY)
matches with 45.00% similarity
= tetrahydropteroyltri-L-glutamate
+ L-methionine
      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     methylation   3 terms 
  Biochemical function     transferase activity     5 terms  


PLoS Biol 3:e31-264 (2005)
PubMed id: 15630480  
Cobalamin-independent methionine synthase (MetE): a face-to-face double barrel that evolved by gene duplication.
R.Pejchal, M.L.Ludwig.
Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy) without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH), both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two (betaalpha)(8) barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys)(3)Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E.Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

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.  
19298181 A.Roth, and R.R.Breaker (2009).
The structural and functional diversity of metabolite-binding riboswitches.
  Annu Rev Biochem, 78, 305-334.  
19286805 E.R.Hondorp, and R.G.Matthews (2009).
Oxidation of cysteine 645 of cobalamin-independent methionine synthase causes a methionine limitation in Escherichia coli.
  J Bacteriol, 191, 3407-3410.  
19208259 Y.Zhang, D.A.Rodionov, M.S.Gelfand, and V.N.Gladyshev (2009).
Comparative genomic analyses of nickel, cobalt and vitamin B12 utilization.
  BMC Genomics, 10, 78.  
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.  
18701702 M.J.Schneider, M.Ulland, and R.D.Sloboda (2008).
A protein methylation pathway in Chlamydomonas flagella is active during flagellar resorption.
  Mol Biol Cell, 19, 4319-4327.  
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
18178732 P.Morris, L.J.Marinelli, D.Jacobs-Sera, R.W.Hendrix, and G.F.Hatfull (2008).
Genomic characterization of mycobacteriophage Giles: evidence for phage acquisition of host DNA by illegitimate recombination.
  J Bacteriol, 190, 2172-2182.  
18804699 S.W.Ragsdale (2008).
Catalysis of methyl group transfers involving tetrahydrofolate and B(12).
  Vitam Horm, 79, 293-324.  
17513866 B.Li, and W.A.van der Donk (2007).
Identification of essential catalytic residues of the cyclase NisC involved in the biosynthesis of nisin.
  J Biol Chem, 282, 21169-21175.  
17898891 F.Rébeillé, S.Ravanel, A.Marquet, R.R.Mendel, M.E.Webb, A.G.Smith, and M.J.Warren (2007).
Roles of vitamins B5, B8, B9, B12 and molybdenum cofactor at cellular and organismal levels.
  Nat Prod Rep, 24, 949-962.  
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.  
17480057 M.Paul, G.C.Patton, and W.A.van der Donk (2007).
Mutants of the zinc ligands of lacticin 481 synthetase retain dehydration activity but have impaired cyclization activity.
  Biochemistry, 46, 6268-6276.  
16527981 B.Li, J.P.Yu, J.S.Brunzelle, G.N.Moll, W.A.van der Donk, and S.K.Nair (2006).
Structure and mechanism of the lantibiotic cyclase involved in nisin biosynthesis.
  Science, 311, 1464-1467.
PDB codes: 2g02 2g0d
17038623 N.Sudarsan, M.C.Hammond, K.F.Block, R.Welz, J.E.Barrick, A.Roth, and R.R.Breaker (2006).
Tandem riboswitch architectures exhibit complex gene control functions.
  Science, 314, 300-304.  
16618097 R.E.Taurog, H.Jakubowski, and R.G.Matthews (2006).
Synergistic, random sequential binding of substrates in cobalamin-independent methionine synthase.
  Biochemistry, 45, 5083-5091.  
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.