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PDBsum entry 2eij

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
2eij
Jmol
Contents
Protein chains
514 a.a. *
227 a.a. *
259 a.a. *
144 a.a. *
105 a.a. *
98 a.a. *
84 a.a. *
79 a.a. *
73 a.a. *
58 a.a. *
49 a.a. *
46 a.a. *
43 a.a. *
Ligands
HEA ×4
TGL ×6
PGV ×8
CUA ×2
PSC ×2
CHD ×8
DMU ×4
PEK ×6
CDL ×4
Metals
_ZN ×4
_CU ×2
_MG ×2
_NA ×2
Waters ×1756
* Residue conservation analysis
PDB id:
2eij
Name: Oxidoreductase
Title: Bovine heart cytochromE C oxidase in the fully reduced state
Structure: CytochromE C oxidase subunit 1. Chain: a, n. Synonym: cytochromE C oxidase polypeptide i. CytochromE C oxidase subunit 2. Chain: b, o. Synonym: cytochromE C oxidase polypeptide ii. CytochromE C oxidase subunit 3. Chain: c, p. Synonym: cytochromE C oxidase polypeptide iii.
Source: Bos taurus. Cattle. Organism_taxid: 9913. Tissue: heart. Tissue: heart
Resolution:
1.90Å     R-factor:   0.206     R-free:   0.234
Authors: K.Muramoto,K.Hirata,K.Shinzawa-Itoh,S.Yoko-O,E.Yamashita,H.A T.Tsukihara,S.Yoshikawa
Key ref:
K.Muramoto et al. (2007). A histidine residue acting as a controlling site for dioxygen reduction and proton pumping by cytochrome c oxidase. Proc Natl Acad Sci U S A, 104, 7881-7886. PubMed id: 17470809 DOI: 10.1073/pnas.0610031104
Date:
13-Mar-07     Release date:   29-May-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00396  (COX1_BOVIN) -  Cytochrome c oxidase subunit 1
Seq:
Struc:
514 a.a.
514 a.a.*
Protein chains
Pfam   ArchSchema ?
P68530  (COX2_BOVIN) -  Cytochrome c oxidase subunit 2
Seq:
Struc:
227 a.a.
227 a.a.*
Protein chains
Pfam   ArchSchema ?
P00415  (COX3_BOVIN) -  Cytochrome c oxidase subunit 3
Seq:
Struc:
261 a.a.
259 a.a.
Protein chains
Pfam   ArchSchema ?
P00423  (COX41_BOVIN) -  Cytochrome c oxidase subunit 4 isoform 1, mitochondrial
Seq:
Struc:
169 a.a.
144 a.a.
Protein chains
Pfam   ArchSchema ?
P00426  (COX5A_BOVIN) -  Cytochrome c oxidase subunit 5A, mitochondrial
Seq:
Struc:
152 a.a.
105 a.a.
Protein chains
Pfam   ArchSchema ?
P00428  (COX5B_BOVIN) -  Cytochrome c oxidase subunit 5B, mitochondrial
Seq:
Struc:
129 a.a.
98 a.a.
Protein chains
Pfam   ArchSchema ?
P07471  (CX6A2_BOVIN) -  Cytochrome c oxidase subunit 6A2, mitochondrial
Seq:
Struc:
97 a.a.
84 a.a.*
Protein chains
Pfam   ArchSchema ?
P00429  (CX6B1_BOVIN) -  Cytochrome c oxidase subunit 6B1
Seq:
Struc:
86 a.a.
79 a.a.
Protein chains
Pfam   ArchSchema ?
P04038  (COX6C_BOVIN) -  Cytochrome c oxidase subunit 6C
Seq:
Struc:
74 a.a.
73 a.a.*
Protein chains
Pfam   ArchSchema ?
P07470  (CX7A1_BOVIN) -  Cytochrome c oxidase subunit 7A1, mitochondrial
Seq:
Struc:
80 a.a.
58 a.a.
Protein chains
Pfam   ArchSchema ?
P13183  (COX7B_BOVIN) -  Cytochrome c oxidase subunit 7B, mitochondrial
Seq:
Struc:
80 a.a.
49 a.a.
Protein chains
Pfam   ArchSchema ?
P00430  (COX7C_BOVIN) -  Cytochrome c oxidase subunit 7C, mitochondrial
Seq:
Struc:
63 a.a.
46 a.a.
Protein chains
Pfam   ArchSchema ?
P10175  (COX8B_BOVIN) -  Cytochrome c oxidase subunit 8B, mitochondrial
Seq:
Struc:
70 a.a.
43 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, N: E.C.1.9.3.1  - Cytochrome-c oxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
4 × ferrocytochrome c
Bound ligand (Het Group name = HEA)
matches with 50.60% similarity
+ O(2)
+ 4 × H(+)
= 4 × ferricytochrome c
+ 2 × H(2)O
      Cofactor: Cu cation
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   11 terms 
  Biological process     oxidation-reduction process   8 terms 
  Biochemical function     electron carrier activity     8 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.0610031104 Proc Natl Acad Sci U S A 104:7881-7886 (2007)
PubMed id: 17470809  
 
 
A histidine residue acting as a controlling site for dioxygen reduction and proton pumping by cytochrome c oxidase.
K.Muramoto, K.Hirata, K.Shinzawa-Itoh, S.Yoko-o, E.Yamashita, H.Aoyama, T.Tsukihara, S.Yoshikawa.
 
  ABSTRACT  
 
Cytochrome c oxidase transfers electrons and protons for dioxygen reduction coupled with proton pumping. These electron and proton transfers are tightly coupled with each other for the effective energy transduction by various unknown mechanisms. Here, we report a coupling mechanism by a histidine (His-503) at the entrance of a proton transfer pathway to the dioxygen reduction site (D-pathway) of bovine heart cytochrome c oxidase. In the reduced state, a water molecule is fixed by hydrogen bonds between His-503 and Asp-91 of the D-pathway and is linked via two water arrays extending to the molecular surface. The microenvironment of Asp-91 appears in the x-ray structure to have a proton affinity as high as that of His-503. Thus, Asp-91 and His-503 cooperatively trap, on the fixed water molecule, the proton that is transferred through the water arrays from the molecular surface. On oxidation, the His-503 imidazole plane rotates by 180 degrees to break the hydrogen bond to the protonated water and releases the proton to Asp-91. On reduction, Asp-91 donates the proton to the dioxygen reduction site through the D-pathway. The proton collection controlled by His-503 was confirmed by partial electron transfer inhibition by binding of Zn2+ and Cd2+ to His-503 in the x-ray structures. The estimated Kd for Zn2+ binding to His-503 in the x-ray structure is consistent with the reported Kd for complete proton-pumping inhibition by Zn2+ [Kannt A, Ostermann T, Muller H, Ruitenberg M (2001) FEBS Lett 503:142-146]. These results suggest that His-503 couples the proton transfer for dioxygen reduction with the proton pumping.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Redox-coupled conformational changes in the His-503–Asp-91 region near the entrance of the D-pathway deduced from the x-ray structures of bovine heart CcO from the 1.8-Å oxidized and 1.9-Å reduced x-ray structures of bovine heart CcO. (a and b) The structures of the D-pathway entrance regions in the reduced and oxidized states shown in stereoviews. The red dotted lines indicate hydrogen bonds that are independent of oxidation state. The blue dotted lines indicate hydrogen bonds that are dependent on the oxidation state. The blue, green, and orange sticks represent the C^ backbones of subunits I, III, and VIIc, respectively. The red spheres represent fixed water molecules. (c and d) Schematic representations of the redox-coupled conformational changes of His-503 in the Cd^2+-free and bound CcO, respectively. The blue and red drawings represent the structures in the reduced and oxidized states, respectively. The black dotted lines represent hydrogen bonds uninfluenced by the oxidation state change. The blue and red dotted lines depict hydrogen bonds appearing in the reduced and oxidized states, respectively. The blue and red thick dotted lines in d represent the coordination bonds that appear in the reduced and oxidized states, respectively.
Figure 5.
Fig. 5. Redox-controlled proton collection and supply by His-503. Only one of the water arrays connecting W207 and W4 and two other possible hydrogen-bonding groups to W207 is shown for the sake of simplicity. The red and blue structures represent the oxidized and reduced (or electron-released and electron-accepted) states of the redox site (or sites) controlling the conformation of the imidazole of His-503. The structures before the oxidation state change are the stable oxidized and reduced states. The circles with arrowheads indicate the rotation of the imidazole group during the transition.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20037139 D.Parul, G.Palmer, and M.Fabian (2010).
Ligand trapping by cytochrome c oxidase: implications for gating at the catalytic center.
  J Biol Chem, 285, 4536-4543.  
20029110 L.Giachini, G.Veronesi, F.Francia, G.Venturoli, and F.Boscherini (2010).
Synergic approach to XAFS analysis for the identification of most probable binding motifs for mononuclear zinc sites in metalloproteins.
  J Synchrotron Radiat, 17, 41-52.  
20533897 P.R.Rich, and A.Maréchal (2010).
The mitochondrial respiratory chain.
  Essays Biochem, 47, 1.  
19767348 R.M.Gawryluk, and M.W.Gray (2010).
An ancient fission of mitochondrial Cox1.
  Mol Biol Evol, 27, 7.  
20396396 Y.Yoshioka, and M.Mitani (2010).
B3LYP study on reduction mechanisms from O2 to H2O at the catalytic sites of fully reduced and mixed-valence bovine cytochrome c oxidases.
  Bioinorg Chem Appl, (), 182804.  
19303362 B.Kadenbach, R.Ramzan, and S.Vogt (2009).
Degenerative diseases, oxidative stress and cytochrome c oxidase function.
  Trends Mol Med, 15, 139-147.  
18664577 E.A.Gorbikova, I.Belevich, M.Wikström, and M.I.Verkhovsky (2008).
The proton donor for O-O bond scission by cytochrome c oxidase.
  Proc Natl Acad Sci U S A, 105, 10733-10737.  
17949262 I.Belevich, and M.I.Verkhovsky (2008).
Molecular mechanism of proton translocation by cytochrome C oxidase.
  Antioxid Redox Signal, 10, 1.  
18830692 M.A.Sharpe, and S.Ferguson-Miller (2008).
A chemically explicit model for the mechanism of proton pumping in heme-copper oxidases.
  J Bioenerg Biomembr, 40, 541-549.  
18975062 P.Brzezinski, and R.B.Gennis (2008).
Cytochrome c oxidase: exciting progress and remaining mysteries.
  J Bioenerg Biomembr, 40, 521-531.  
18692465 R.E.Green, A.S.Malaspinas, J.Krause, A.W.Briggs, P.L.Johnson, C.Uhler, M.Meyer, J.M.Good, T.Maricic, U.Stenzel, K.Prüfer, M.Siebauer, H.A.Burbano, M.Ronan, J.M.Rothberg, M.Egholm, P.Rudan, D.Brajković, Z.Kućan, I.Gusić, M.Wikström, L.Laakkonen, J.Kelso, M.Slatkin, and S.Pääbo (2008).
A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing.
  Cell, 134, 416-426.  
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.