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PDBsum entry 1x6m

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
1x6m
Jmol
Contents
Protein chains
196 a.a. *
Ligands
SO4 ×7
GOL ×5
Metals
_ZN ×8
Waters ×255
* Residue conservation analysis
PDB id:
1x6m
Name: Lyase
Title: Crystal structure of the glutathione-dependent formaldehyde- enzyme (gfa)
Structure: Glutathione-dependent formaldehyde-activating enz chain: a, b, c, d. Synonym: gfa. Engineered: yes
Source: Paracoccus denitrificans. Organism_taxid: 266. Gene: gfa. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
2.35Å     R-factor:   0.193     R-free:   0.250
Authors: A.M.Neculai,D.Neculai,J.A.Vorholt,S.Becker
Key ref:
A.M.Neculai et al. (2005). A dynamic zinc redox switch. J Biol Chem, 280, 2826-2830. PubMed id: 15548539 DOI: 10.1074/jbc.C400517200
Date:
11-Aug-04     Release date:   23-Nov-04    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q51669  (GFA_PARDE) -  Glutathione-dependent formaldehyde-activating enzyme
Seq:
Struc:
194 a.a.
196 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.4.1.22  - S-(hydroxymethyl)glutathione synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-(hydroxymethyl)glutathione = glutathione + formaldehyde
S-(hydroxymethyl)glutathione
= glutathione
+ formaldehyde
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   2 terms 
  Biochemical function     lyase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.C400517200 J Biol Chem 280:2826-2830 (2005)
PubMed id: 15548539  
 
 
A dynamic zinc redox switch.
A.M.Neculai, D.Neculai, C.Griesinger, J.A.Vorholt, S.Becker.
 
  ABSTRACT  
 
The crystal structures of glutathione-dependent formaldehyde-activating enzyme (Gfa) from Paracoccus denitrificans, which catalyzes the formation of S-hydroxymethylglutathione from formaldehyde and glutathione, and its complex with glutathione (Gfa-GTT) have been determined. Gfa has a new fold with two zinc-sulfur centers, one that is structural (zinc tetracoordinated) and one catalytic (zinc apparently tricoordinated). In Gfa-GTT, the catalytic zinc is displaced due to disulfide bond formation of glutathione with one of the zinc-coordinating cysteines. Soaking crystals of Gfa-GTT with formaldehyde restores the holoenzyme. Accordingly, the displaced zinc forms a complex by scavenging formaldehyde and glutathione. The activation of formaldehyde and of glutathione in this zinc complex favors the final nucleophilic addition, followed by relocation of zinc in the catalytic site. Therefore, the structures of Gfa and Gfa-GTT draw the critical association between a dynamic zinc redox switch and a nucleophilic addition as a new facet of the redox activity of zinc-sulfur sites.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. Ribbon representation of the Gfa dimer. The molecules are colored according to their secondary structures: helices are in red ( 1, 7, 8), including the 3[10] helices ( 2, 3, 4, 6 (the latter is not visible within the same monomer and is assigned in the other monomer); the extended eight-stranded -sheet ( 6, 7, 8, 9, 4, 3, 10, 10, 11) sandwiched with the triple-stranded -sheet ( 1, 2, [197]{beta} 5) is in blue.
Figure 2.
FIG. 2. a and b, view of the catalytic site of Gfa (a) and Gfa-GTT (b) including the H-bonding network (dotted lines) in which the zinc-coordinating thiol groups are involved. The residues involved in Zn2 (a) and GTT (b) binding are labeled accordingly. The representation also contains the electron density at 1 level in the 2F[o] - F[c] map for the catalytic zinc and the Cys residues in Gfa (a) and for Cys residues and GTT in Gfa-GTT (B). To evaluate the changes upon GTT coordination, we chose similar perspectives of the active site. Numbering of the residues is according to the expression construct that contains three additional amino acids at the N terminus. c, electron density contoured at 3 level in the F[o] - F[c] map (in green) at the catalytic site of Gfa-GTT soaked with formaldehyde.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 2826-2830) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19930468 Z.Honda, T.Suzuki, and H.Honda (2009).
Identification of CENP-V as a novel microtubule-associating molecule that activates Src family kinases through SH3 domain interaction.
  Genes Cells, 14, 1383-1394.  
18772885 A.M.Tadeu, S.Ribeiro, J.Johnston, I.Goldberg, D.Gerloff, and W.C.Earnshaw (2008).
CENP-V is required for centromere organization, chromosome alignment and cytokinesis.
  EMBO J, 27, 2510-2522.  
18174148 S.M.Wilson, M.P.Gleisten, and T.J.Donohue (2008).
Identification of proteins involved in formaldehyde metabolism by Rhodobacter sphaeroides.
  Microbiology, 154, 296-305.  
17331952 G.Wang, C.Strang, P.J.Pfaffinger, and M.Covarrubias (2007).
Zn2+-dependent redox switch in the intracellular T1-T1 interface of a Kv channel.
  J Biol Chem, 282, 13637-13647.  
16987000 W.Maret (2006).
Zinc coordination environments in proteins as redox sensors and signal transducers.
  Antioxid Redox Signal, 8, 1419-1441.  
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