spacer
spacer

PDBsum entry 2bs2

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
2bs2
Jmol
Contents
Protein chains
656 a.a. *
240 a.a. *
255 a.a. *
Ligands
FAD ×2
FUM ×2
FES ×2
F3S ×2
SF4 ×2
HEM ×4
LMT ×2
Metals
_NA ×2
Waters ×990
* Residue conservation analysis
PDB id:
2bs2
Name: Oxidoreductase
Title: Quinol:fumarate reductase from wolinella succinogenes
Structure: Quinol-fumarate reductase flavoprotein subunit a. Chain: a, d. Other_details: fad covalently bound to his a43 by an 8- alpha-(n-epsilon-histidyl) bond. Quinol-fumarate reductase iron-sulfur subunit b. Chain: b, e. Quinol-fumarate reductase diheme cytochrome b subunit c. Chain: c, f.
Source: Wolinella succinogenes. Organism_taxid: 844. Organism_taxid: 844
Biol. unit: Hexamer (from PDB file)
Resolution:
1.78Å     R-factor:   0.229     R-free:   0.237
Authors: C.R.D.Lancaster
Key ref:
M.G.Madej et al. (2006). Evidence for transmembrane proton transfer in a dihaem-containing membrane protein complex. EMBO J, 25, 4963-4970. PubMed id: 17024183 DOI: 10.1038/sj.emboj.7601361
Date:
14-May-05     Release date:   25-Oct-06    
Supersedes: 1qla
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P17412  (FRDA_WOLSU) -  Fumarate reductase flavoprotein subunit
Seq:
Struc:
 
Seq:
Struc:
656 a.a.
656 a.a.
Protein chains
Pfam   ArchSchema ?
P17596  (FRDB_WOLSU) -  Fumarate reductase iron-sulfur subunit
Seq:
Struc:
239 a.a.
240 a.a.
Protein chains
Pfam   ArchSchema ?
P17413  (FRDC_WOLSU) -  Fumarate reductase cytochrome b subunit
Seq:
Struc:
256 a.a.
255 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 2: Chains A, D: E.C.1.3.5.4  - Fumarate reductase (quinol).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Succinate + a quinone = fumarate + a quinol
Succinate
Bound ligand (Het Group name = FUM)
corresponds exactly
+ quinone
= fumarate
+ quinol
   Enzyme class 3: Chains B, E: E.C.1.3.5.1  - Succinate dehydrogenase (quinone).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
      Reaction: Succinate + a quinone = fumarate + a quinol
Succinate
+ quinone
= fumarate
+ quinol
      Cofactor: FAD; Iron-sulfur
FAD
Iron-sulfur
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   4 terms 
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     electron carrier activity     10 terms  

 

 
    reference    
 
 
DOI no: 10.1038/sj.emboj.7601361 EMBO J 25:4963-4970 (2006)
PubMed id: 17024183  
 
 
Evidence for transmembrane proton transfer in a dihaem-containing membrane protein complex.
M.G.Madej, H.R.Nasiri, N.S.Hilgendorff, H.Schwalbe, C.R.Lancaster.
 
  ABSTRACT  
 
Membrane protein complexes can support both the generation and utilisation of a transmembrane electrochemical proton potential ('proton-motive force'), either by transmembrane electron transfer coupled to protolytic reactions on opposite sides of the membrane or by transmembrane proton transfer. Here we provide the first evidence that both of these mechanisms are combined in the case of a specific respiratory membrane protein complex, the dihaem-containing quinol:fumarate reductase (QFR) of Wolinella succinogenes, so as to facilitate transmembrane electron transfer by transmembrane proton transfer. We also demonstrate the non-functionality of this novel transmembrane proton transfer pathway ('E-pathway') in a variant QFR where a key glutamate residue has been replaced. The 'E-pathway', discussed on the basis of the 1.78-Angstrom-resolution crystal structure of QFR, can be concluded to be essential also for the viability of pathogenic varepsilon-proteobacteria such as Helicobacter pylori and is possibly relevant to proton transfer in other dihaem-containing membrane proteins, performing very different physiological functions.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Addition of the uncoupler CCCP stimulates the oxidation of DMNH[2] by fumarate as catalysed by proteoliposomal E180Q-QFR. (A) Non-functionality of the 'E-pathway' gives rise to electrogenicity of E180Q-QFR. Subunit A is shown in blue, subunit B in orange, and subunit C in green. The haem groups are shown as yellow diamonds, with the upper haem corresponding to b[P] and the lower one to b[D]. Protons bound are shown in red, protons released in green. (B) Overall electroneutrality in wild-type QFR as explained by the 'E-pathway'. For clarity, protons are indicated to be released to and taken up from the bulk solvent phase on both sides of the membrane. However, it can presently not be ruled out that, on either side of the membrane, the protons are transported along the protein surface from the respective proton exit sites to those of proton entry, without being released to the bulk, as argued elsewhere (Mulkidjanian et al, 2006). (C) DMNH[2] oxidation as (not) catalysed by E180Q-QFR reconstituted in proteoliposomes (500 g). The traces were recorded under the same conditions as for Figure 2A, except that DMNH[2] (20 M) was used as the electron donor and the fumarate concentration was 40 M. Catalytic activity was significantly detectable only after the addition of 25 M of the protonophore CCCP. (D) Enlarged section of the left half of (C). Linear fit of the data points of A at t<16 s (grey) and t>16 s (red).
Figure 3.
Figure 3 The 'E-pathway' in dihaem-containing QFR. Possible elements of the 'E-pathway' as observed in the crystal structure of wild-type QFR refined at 1.78 Å resolution (PDB entry 2BS2). To facilitate orientation between various panels, dashed light blue lines connect the hydroxyl group of residue Tyr C245 to the N epsilon atom of His-B215 and the hydroxyl group of Tyr C231 to the C atom of the b[D] ring C propionate. Along these dashed lines, a large number of polar and protonatable residues can be found. (A, B (stereo)) Perpendicular views with the periplasm at the bottom, the cytoplasm at the top and the membrane spanning region indicated by the two haem groups. In general, carbon, nitrogen and oxygen atoms are shown in yellow, blue and red, respectively. In the case of Glu C180, the 'distal' conformer contains light blue carbon atoms. The groups whose role in such an 'E-pathway' has received experimental support, Glu C180 (Lancaster et al, 2005; Haas et al, 2005) and the b[D] ring C propionate (Mileni et al, 2005) are highlighted by purple ellipsoids. The 2|F[o]|-|F[c]| electron density map, contoured at 1.0 standard deviations ( ) above the mean density of the map, is shown in blue for the protein and in green for non-protein groups such as haem groups and water molecules. (C, D) The transmembrane region as viewed from the cytoplasmic side. (C) A schematic representation of the packing of transmembrane helices V and VI, whereas (D) (stereo) depicts the corresponding view in the structure. The residues shown on transmembrane helix V are Glu C180 (alternate conformers), Ser C184 and Tyr C188. Residues shown on transmembrane helix VI are Tyr C231, Ser C217, Thr C214, Lys C213, Lys C210, Arg C206 and Asp C203. The residue shown on transmembrane helix IV is Asp C122.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2006, 25, 4963-4970) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20938980 K.Illergård, A.Kauko, and A.Elofsson (2011).
Why are polar residues within the membrane core evolutionary conserved?
  Proteins, 79, 79-91.  
19826804 K.McLuskey, A.W.Roszak, Y.Zhu, and N.W.Isaacs (2010).
Crystal structures of all-alpha type membrane proteins.
  Eur Biophys J, 39, 723-755.  
20331424 N.V.Azarkina, and A.A.Konstantinov (2010).
Energization of Bacillus subtilis membrane vesicles increases catalytic activity of succinate:menaquinone oxidoreductase.
  Biochemistry (Mosc), 75, 50-62.  
19170876 H.D.Juhnke, H.Hiltscher, H.R.Nasiri, H.Schwalbe, and C.R.Lancaster (2009).
Production, characterization and determination of the real catalytic properties of the putative 'succinate dehydrogenase' from Wolinella succinogenes.
  Mol Microbiol, 71, 1088-1101.  
18418633 E.A.Berry, and F.A.Walker (2008).
Bis-histidine-coordinated hemes in four-helix bundles: how the geometry of the bundle controls the axial imidazole plane orientations in transmembrane cytochromes of mitochondrial complexes II and III and related proteins.
  J Biol Inorg Chem, 13, 481-498.  
18385138 T.M.Tomasiak, E.Maklashina, G.Cecchini, and T.M.Iverson (2008).
A threonine on the active site loop controls transition state formation in Escherichia coli respiratory complex II.
  J Biol Chem, 283, 15460-15468.
PDB code: 3cir
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.