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PDBsum entry 2gsm

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
2gsm
Jmol
Contents
Protein chains
535 a.a. *
256 a.a. *
Ligands
DMU ×10
_OH ×2
HEA ×4
TRD ×12
Metals
_CU ×6
_MG ×2
_CA ×2
_CD ×4
Waters ×503
* Residue conservation analysis
PDB id:
2gsm
Name: Oxidoreductase
Title: Catalytic core (subunits i and ii) of cytochromE C oxidase f rhodobacter sphaeroides
Structure: CytochromE C oxidase subunit 1. Chain: a, c. Synonym: cytochromE C oxidase polypeptide i, cytochrome aa3 1. Engineered: yes. CytochromE C oxidase subunit 2. Chain: b, d. Synonym: cytochromE C oxidase polypeptide ii, cytochrome aa 2, oxidase aa3, subunit 2.
Source: Rhodobacter sphaeroides. Organism_taxid: 1063. Gene: ctad. Expressed in: rhodobacter sphaeroides. Expression_system_taxid: 1063. Gene: ctac, coxii, ctab. Expression_system_taxid: 1063
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.214     R-free:   0.232
Authors: L.Qin,C.Hiser,A.Mulichak,R.M.Garavito,S.Ferguson-Miller
Key ref:
L.Qin et al. (2006). Identification of conserved lipid/detergent-binding sites in a high-resolution structure of the membrane protein cytochrome c oxidase. Proc Natl Acad Sci U S A, 103, 16117-16122. PubMed id: 17050688 DOI: 10.1073/pnas.0606149103
Date:
26-Apr-06     Release date:   10-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P33517  (COX1_RHOSH) -  Cytochrome c oxidase subunit 1
Seq:
Struc:
 
Seq:
Struc:
566 a.a.
535 a.a.
Protein chains
Pfam   ArchSchema ?
Q03736  (COX2_RHOSH) -  Cytochrome c oxidase subunit 2
Seq:
Struc:
303 a.a.
256 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: 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   4 terms 
  Biological process     oxidation-reduction process   8 terms 
  Biochemical function     electron carrier activity     7 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.0606149103 Proc Natl Acad Sci U S A 103:16117-16122 (2006)
PubMed id: 17050688  
 
 
Identification of conserved lipid/detergent-binding sites in a high-resolution structure of the membrane protein cytochrome c oxidase.
L.Qin, C.Hiser, A.Mulichak, R.M.Garavito, S.Ferguson-Miller.
 
  ABSTRACT  
 
Well ordered reproducible crystals of cytochrome c oxidase (CcO) from Rhodobacter sphaeroides yield a previously unreported structure at 2.0 A resolution that contains the two catalytic subunits and a number of alkyl chains of lipids and detergents. Comparison with crystal structures of other bacterial and mammalian CcOs reveals that the positions occupied by native membrane lipids and detergent substitutes are highly conserved, along with amino acid residues in their vicinity, suggesting a more prevalent and specific role of lipid in membrane protein structure than often envisioned. Well defined detergent head groups (maltose) are found associated with aromatic residues in a manner similar to phospholipid head groups, likely contributing to the success of alkyl glycoside detergents in supporting membrane protein activity and crystallizability. Other significant features of this structure include the following: finding of a previously unreported crystal contact mediated by cadmium and an engineered histidine tag; documentation of the unique His-Tyr covalent linkage close to the active site; remarkable conservation of a chain of waters in one proton pathway (D-path); and discovery of an inhibitory cadmium-binding site at the entrance to another proton path (K-path). These observations provide important insight into CcO structure and mechanism, as well as the significance of bound lipid in membrane proteins.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Important structural features of the two-subunit RsCcO. Subunit I is shown in yellow, and subunit II is shown in green. Residues of interest are shown in stick models and colored blue, except for Q142[II], which is colored magenta for clarity. Heme groups are shown in salmon. Metals are shown as spheres and colored as follows: Fe, salmon; Cu, red; Mg, blue; Cd, magenta. Two proton uptake pathways are indicated by dotted arrows, with resolved waters in the D path shown as blue spheres. One of the resolved detergent molecules (DM-decyl maltoside), corresponding to the DM at the phosphatidyl choline (PC) site in Fig. 3C, is shown in cyan, as is one of the alkyl chains corresponding to the cardiolipin (CDL) site in Fig. 3B.
Figure 4.
Fig. 4. Characteristics of detergent molecules resolved in the I-II RsCcO structure. (A) Two decyl maltoside detergent molecules (colored by atom type: C, green; O, red; N, blue) resolved at the interface of two RsCcO molecules (gray and wheat). The (2F[o] – F[c]) difference electron density map (dark blue) surrounding the decyl maltosides contoured at 1.3 is shown. Tyrosine and tryptophan residues (blue) were found stacking with the head groups of the two decyl maltosides. (B) One decyl maltoside resolved on another location, also at molecular interface. The (2F[o] – F[c]) difference electron density map (dark blue) contoured at 1.0 is shown. Phenylalanine residue (blue) was found forming a stacking interaction with the sugar ring.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21286652 A.V.Dyuba, A.M.Arutyunyan, T.V.Vygodina, N.V.Azarkina, A.V.Kalinovich, Y.A.Sharonov, and A.A.Konstantinov (2011).
Circular dichroism spectra of cytochrome c oxidase.
  Metallomics, 3, 417-432.  
21368144 I.von der Hocht, J.H.van Wonderen, F.Hilbers, H.Angerer, F.Macmillan, and H.Michel (2011).
Interconversions of P and F intermediates of cytochrome c oxidase from Paracoccus denitrificans.
  Proc Natl Acad Sci U S A, 108, 3964-3969.  
21205904 J.Liu, L.Qin, and S.Ferguson-Miller (2011).
Crystallographic and online spectral evidence for role of conformational change and conserved water in cytochrome oxidase proton pump.
  Proc Natl Acad Sci U S A, 108, 1284-1289.
PDB codes: 3om3 3oma 3omi 3omn
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.  
20826347 J.A.Cuesta-Seijo, C.Neale, M.A.Khan, J.Moktar, C.D.Tran, R.E.Bishop, R.Pomès, and G.G.Privé (2010).
PagP crystallized from SDS/cosolvent reveals the route for phospholipid access to the hydrocarbon ruler.
  Structure, 18, 1210-1219.
PDB code: 3gp6
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.  
20667175 K.R.Vinothkumar, and R.Henderson (2010).
Structures of membrane proteins.
  Q Rev Biophys, 43, 65.  
20798065 L.N.Ojemyr, H.J.Lee, R.B.Gennis, and P.Brzezinski (2010).
Functional interactions between membrane-bound transporters and membranes.
  Proc Natl Acad Sci U S A, 107, 15763-15767.  
20192226 S.A.Siletsky, J.Zhu, R.B.Gennis, and A.A.Konstantinov (2010).
Partial steps of charge translocation in the nonpumping N139L mutant of Rhodobacter sphaeroides cytochrome c oxidase with a blocked D-channel.
  Biochemistry, 49, 3060-3073.  
20576851 S.Buschmann, E.Warkentin, H.Xie, J.D.Langer, U.Ermler, and H.Michel (2010).
The structure of cbb3 cytochrome oxidase provides insights into proton pumping.
  Science, 329, 327-330.
PDB code: 3mk7
20058880 X.Zhang, E.Y.Chien, M.J.Chalmers, B.D.Pascal, J.Gatchalian, R.C.Stevens, and P.R.Griffin (2010).
Dynamics of the beta2-adrenergic G-protein coupled receptor revealed by hydrogen-deuterium exchange.
  Anal Chem, 82, 1100-1108.  
19164527 H.Aoyama, K.Muramoto, K.Shinzawa-Itoh, K.Hirata, E.Yamashita, T.Tsukihara, T.Ogura, and S.Yoshikawa (2009).
A peroxide bridge between Fe and Cu ions in the O2 reduction site of fully oxidized cytochrome c oxidase could suppress the proton pump.
  Proc Natl Acad Sci U S A, 106, 2165-2169.
PDB codes: 2zxw 3abl 3abm
19218458 I.Namslauer, and P.Brzezinski (2009).
A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase.
  Proc Natl Acad Sci U S A, 106, 3402-3407.  
19551800 J.M.Alakoskela, P.Vitovic, and P.K.Kinnunen (2009).
Screening for the drug-phospholipid interaction: correlation to phospholipidosis.
  ChemMedChem, 4, 1224-1251.  
19146411 L.A.Abriata, G.N.Ledesma, R.Pierattelli, and A.J.Vila (2009).
Electronic structure of the ground and excited states of the Cu(A) site by NMR spectroscopy.
  J Am Chem Soc, 131, 1939-1946.  
19348907 L.Geren, B.Durham, and F.Millett (2009).
Chapter 28 Use of ruthenium photoreduction techniques to study electron transfer in cytochrome oxidase.
  Methods Enzymol, 456, 507-520.  
19397279 L.Qin, J.Liu, D.A.Mills, D.A.Proshlyakov, C.Hiser, and S.Ferguson-Miller (2009).
Redox-dependent conformational changes in cytochrome C oxidase suggest a gating mechanism for proton uptake.
  Biochemistry, 48, 5121-5130.
PDB codes: 3fye 3fyi
19108635 M.A.Sharpe, M.D.Krzyaniak, S.Xu, J.McCracken, and S.Ferguson-Miller (2009).
EPR evidence of cyanide binding to the Mn(Mg) center of cytochrome c oxidase: support for Cu(A)-Mg involvement in proton pumping.
  Biochemistry, 48, 328-335.  
18981182 M.Wikström, A.A.Kelly, A.Georgiev, H.M.Eriksson, M.R.Klement, M.Bogdanov, W.Dowhan, and A.Wieslander (2009).
Lipid-engineered Escherichia coli membranes reveal critical lipid headgroup size for protein function.
  J Biol Chem, 284, 954-965.  
19252222 V.Rauhamäki, D.A.Bloch, M.I.Verkhovsky, and M.Wikström (2009).
Active site of cytochrome cbb3.
  J Biol Chem, 284, 11301-11308.  
19666617 Y.C.Kim, M.Wikström, and G.Hummer (2009).
Kinetic gating of the proton pump in cytochrome c oxidase.
  Proc Natl Acad Sci U S A, 106, 13707-13712.  
18214963 A.C.Freydank, W.Brandt, and B.Dräger (2008).
Protein structure modeling indicates hexahistidine-tag interference with enzyme activity.
  Proteins, 72, 173-183.  
18847227 D.A.Mills, S.Xu, L.Geren, C.Hiser, L.Qin, M.A.Sharpe, J.McCracken, B.Durham, F.Millett, and S.Ferguson-Miller (2008).
Proton-dependent electron transfer from CuA to heme a and altered EPR spectra in mutants close to heme a of cytochrome oxidase.
  Biochemistry, 47, 11499-11509.  
18753631 D.N.Ho, N.C.Pomroy, J.A.Cuesta-Seijo, and G.G.Privé (2008).
Crystal structure of a self-assembling lipopeptide detergent at 1.20 A.
  Proc Natl Acad Sci U S A, 105, 12861-12866.
PDB code: 3cay
17949262 I.Belevich, and M.I.Verkhovsky (2008).
Molecular mechanism of proton translocation by cytochrome C oxidase.
  Antioxid Redox Signal, 10, 1.  
18202628 J.M.Boncella (2008).
Inorganic chemistry: uranium gets a reaction.
  Nature, 451, 250-252.  
18155154 J.Xu, and G.A.Voth (2008).
Redox-coupled proton pumping in cytochrome c oxidase: further insights from computer simulation.
  Biochim Biophys Acta, 1777, 196-201.  
18759498 L.Qin, D.A.Mills, L.Buhrow, C.Hiser, and S.Ferguson-Miller (2008).
A conserved steroid binding site in cytochrome C oxidase.
  Biochemistry, 47, 9931-9933.
PDB code: 3dtu
18975062 P.Brzezinski, and R.B.Gennis (2008).
Cytochrome c oxidase: exciting progress and remaining mysteries.
  J Bioenerg Biomembr, 40, 521-531.  
18430799 V.R.Kaila, M.I.Verkhovsky, G.Hummer, and M.Wikström (2008).
Glutamic acid 242 is a valve in the proton pump of cytochrome c oxidase.
  Proc Natl Acad Sci U S A, 105, 6255-6259.  
  18084085 B.Liu, V.M.Luna, Y.Chen, C.D.Stout, and J.A.Fee (2007).
An unexpected outcome of surface engineering an integral membrane protein: improved crystallization of cytochrome ba(3) from Thermus thermophilus.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 1029-1034.
PDB codes: 2qpd 2qpe
17429993 J.M.Swanson, C.M.Maupin, H.Chen, M.K.Petersen, J.Xu, Y.Wu, and G.A.Voth (2007).
Proton solvation and transport in aqueous and biomolecular systems: insights from computer simulations.
  J Phys Chem B, 111, 4300-4314.  
17309257 J.Xu, M.A.Sharpe, L.Qin, S.Ferguson-Miller, and G.A.Voth (2007).
Storage of an excess proton in the hydrogen-bonded network of the d-pathway of cytochrome C oxidase: identification of a protonated water cluster.
  J Am Chem Soc, 129, 2910-2913.  
17470809 K.Muramoto, K.Hirata, K.Shinzawa-Itoh, S.Yoko-o, E.Yamashita, H.Aoyama, T.Tsukihara, and S.Yoshikawa (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.
PDB codes: 2eij 2eik 2eil 2eim 2ein
17360500 K.Shimokata, Y.Katayama, H.Murayama, M.Suematsu, T.Tsukihara, K.Muramoto, H.Aoyama, S.Yoshikawa, and H.Shimada (2007).
The proton pumping pathway of bovine heart cytochrome c oxidase.
  Proc Natl Acad Sci U S A, 104, 4200-4205.  
17477548 L.Qin, D.A.Mills, C.Hiser, A.Murphree, R.M.Garavito, S.Ferguson-Miller, and J.Hosler (2007).
Crystallographic location and mutational analysis of Zn and Cd inhibitory sites and role of lipidic carboxylates in rescuing proton path mutants in cytochrome c oxidase.
  Biochemistry, 46, 6239-6248.  
17719219 L.Qin, M.A.Sharpe, R.M.Garavito, and S.Ferguson-Miller (2007).
Conserved lipid-binding sites in membrane proteins: a focus on cytochrome c oxidase.
  Curr Opin Struct Biol, 17, 444-450.  
  17554166 M.Murakami, R.Kitahara, T.Gotoh, and T.Kouyama (2007).
Crystallization and crystal properties of squid rhodopsin.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 475-479.  
18021062 P.Nicholls (2007).
The oxygenase-peroxidase theory of Bach and Chodat and its modern equivalents: change and permanence in scientific thinking as shown by our understanding of the roles of water, peroxide, and oxygen in the functioning of redox enzymes.
  Biochemistry (Mosc), 72, 1039-1046.  
18021064 T.V.Vygodina, and A.A.Konstantinov (2007).
Peroxidase activity of mitochondrial cytochrome c oxidase.
  Biochemistry (Mosc), 72, 1056-1064.  
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.