DB code: M00194

RLCP classification 10.100110.100.10300 : Electron transfer
10.12100.110.10080 : Electron transfer
10.100012.100.10290 : Electron transfer
CATH domain 1.20.210.10 : Cytochrome C Oxidase; Chain A Catalytic domain
1.20.1070.10 : Rhopdopsin 7-helix transmembrane proteins
2.60.40.420 : Immunoglobulin-like Catalytic domain
1.-.-.- :
E.C. 1.9.3.1
CSA 1ehk
M-CSA 1ehk
MACiE

CATH domain Related DB codes (homologues)
1.20.210.10 : Cytochrome C Oxidase; Chain A M00062
2.60.40.420 : Immunoglobulin-like T00215 T00216 M00115 M00062

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
Q56408 Cytochrome c oxidase subunit 1
EC 1.9.3.1
Cytochrome c ba(3) subunit I
Cytochrome c oxidase polypeptide I
Cytochrome cba3 subunit 1
PF00115 (COX1)
[Graphical View]
Q5SJ79 Cytochrome c oxidase subunit 1
EC 1.9.3.1
Cytochrome c ba(3) subunit I
Cytochrome c oxidase polypeptide I
Cytochrome cba3 subunit 1
PF00115 (COX1)
[Graphical View]
YP_144401.1 (Protein)
NC_006461.1 (DNA/RNA sequence)
P98052 Cytochrome c oxidase subunit 2
EC 1.9.3.1
Cytochrome c ba(3) subunit II
Cytochrome c oxidase polypeptide II
Cytochrome cba3 subunit 2
PF00116 (COX2)
[Graphical View]
Q5SJ80 Cytochrome c oxidase subunit 2
EC 1.9.3.1
Cytochrome c ba(3) subunit II
Cytochrome c oxidase polypeptide II
Cytochrome cba3 subunit 2
PF00116 (COX2)
PF09125 (COX2-transmemb)
[Graphical View]
YP_144400.1 (Protein)
NC_006461.1 (DNA/RNA sequence)
P82543 Cytochrome c oxidase polypeptide 2A
EC 1.9.3.1
Cytochrome c ba(3) subunit IIA
Cytochrome c oxidase polypeptide IIA
Cytochrome cba3 subunit 2A
PF08113 (CoxIIa)
[Graphical View]
YP_144399.1 (Protein)
NC_006461.1 (DNA/RNA sequence)

KEGG enzyme name
cytochrome-c oxidase
cytochrome oxidase
cytochrome a3
cytochrome aa3
Warburg's respiratory enzyme
indophenol oxidase
indophenolase
complex IV (mitochondrial electron transport)
ferrocytochrome c oxidase
NADH cytochrome c oxidase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q56408 COX1_THETH 4 ferrocytochrome c + O(2) + 4 H(+) = 4 ferricytochrome c + 2 H(2)O. Cell membrane, Multi-pass membrane protein (By similarity). Binds 2 heme groups (By similarity). Copper B (By similarity).
Q5SJ79 COX1_THET8 4 ferrocytochrome c + O(2) + 4 H(+) = 4 ferricytochrome c + 2 H(2)O. Cell membrane, Multi-pass membrane protein. Binds 2 heme groups (By similarity). Copper B (By similarity).
P98052 COX2_THETH 4 ferrocytochrome c + O(2) + 4 H(+) = 4 ferricytochrome c + 2 H(2)O. Cell membrane, Peripheral membrane protein.
Q5SJ80 COX2_THET8 4 ferrocytochrome c + O(2) + 4 H(+) = 4 ferricytochrome c + 2 H(2)O. Cell membrane, Single-pass membrane protein.
P82543 COXA_THET8 4 ferrocytochrome c + O(2) + 4 H(+) = 4 ferricytochrome c + 2 H(2)O. Cell membrane, Single-pass membrane protein.

KEGG Pathways
Map code Pathways E.C.
MAP00190 Oxidative phosphorylation

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00070 C00032 C00032 C00126 C00007 C00125 C00001
E.C.
Compound Copper Heme A Heme A3 Ferrocytochrome c O2 Ferricytochrome c H2O
Type heavy metal aromatic ring (with nitrogen atoms),carboxyl group,heavy metal aromatic ring (with nitrogen atoms),carboxyl group,heavy metal amide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide group others amide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide group H2O
ChEBI 28694
30052
17627
26355
17627
26355
15379
26689
27140
15377
PubChem 23978
977
22247451
962
1xmeA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CU Analogue:HEM Analogue:HAS Unbound Unbound Unbound
1ehkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CU Analogue:HEM Analogue:HAS Unbound Unbound Unbound
1xmeB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1ehkB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
2fwlB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1xmeB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:CUA Unbound Unbound Unbound Unbound Unbound
1ehkB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:CUA Unbound Unbound Unbound Unbound Unbound
2fwlB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:CUA Unbound Unbound Bound:HEC (chain A) Unbound Unbound
2cuaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:CUA Unbound Unbound Unbound Unbound Unbound
2cuaB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:CUA Unbound Unbound Unbound Unbound Unbound
1xmeC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1ehkC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1xmeA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 384;HIS 386 HIS 384(Heme A3 Fe1 binding);HIS 72;HIS 386(Heme A Fe2 binding);HIS 233;HIS 282;HIS 283(Cu binding) PHE 385;ARG 449;ARG 450
1ehkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 384;HIS 386 HIS 384(Heme A3 Fe1 binding);HIS 72;HIS 386(Heme A Fe2 binding);HIS 233;HIS 282;HIS 283(Cu binding) PHE 385;ARG 449;ARG 450
1xmeB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ehkB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2fwlB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1xmeB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain PHE 88;HIS 157 HIS 114;CYS 149;GLN 151;CYS 153;HIS 157;MET 160(dinuclear Cu binding) ALA 87;PHE 88
1ehkB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain PHE 88;HIS 157 HIS 114;CYS 149;GLN 151;CYS 153;HIS 157;MET 160(dinuclear Cu binding) ALA 87;PHE 88
2fwlB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain PHE 88;HIS 157 HIS 114;CYS 149;GLN 151;CYS 153;HIS 157;MET 160(dinuclear Cu binding) ALA 87;PHE 88
2cuaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain PHE 88;HIS 157 HIS 114;CYS 149;GLN 151;CYS 153;HIS 157;MET 160(dinuclear Cu binding) ALA 87;PHE 88
2cuaB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain PHE 88;HIS 157 HIS 114;CYS 149;GLN 151;CYS 153;HIS 157;MET 160(dinuclear Cu binding) ALA 87;PHE 88
1xmeC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ehkC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[8]
p.1770-1773
[11]
Fig.10, p.14511-14512

References
[1]
Resource
Comments
Medline ID
PubMed ID 7615066
Journal FEBS Lett
Year 1995
Volume 368
Pages 132-4
Authors Soulimane T, Gohlke U, Huber R, Buse G
Title Three-dimensional crystals of cytochrome-c oxidase from Thermus thermophilus diffracting to 3.8 A resolution.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9399580
Journal J Biochem (Tokyo)
Year 1997
Volume 122
Pages 764-71
Authors Sakamoto J, Handa Y, Sone N
Title A novel cytochrome b(o/a)3-type oxidase from Bacillus stearothermophilus catalyzes cytochrome c-551 oxidation.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9299406
Journal Biochem Biophys Res Commun
Year 1997
Volume 237
Pages 572-6
Authors Soulimane T, von Walter M, Hof P, Than ME, Huber R, Buse G
Title Cytochrome-c552 from Thermus thermophilus: a functional and crystallographic investigation.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9281430
Journal J Mol Biol
Year 1997
Volume 271
Pages 629-44
Authors Than ME, Hof P, Huber R, Bourenkov GP, Bartunik HD, Buse G, Soulimane T
Title Thermus thermophilus cytochrome-c552: A new highly thermostable cytochrome-c structure obtained by MAD phasing.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10486572
Journal FEBS Lett
Year 1999
Volume 457
Pages 98-102
Authors Siletskiy S, Soulimane T, Azarkina N, Vygodina TV, Buse G, Kaulen A, Konstantinov A
Title Time-resolved generation of a membrane potential by ba3 cytochrome c oxidase from Thermus thermophilus. Evidence for reduction-induced opening of the binuclear center.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS)
Medline ID 99287095
PubMed ID 10360350
Journal Nat Struct Biol
Year 1999
Volume 6
Pages 509-16
Authors Williams PA, Blackburn NJ, Sanders D, Bellamy H, Stura EA, Fee JA, McRee DE
Title The CuA domain of Thermus thermophilus ba3-type cytochrome c oxidase at 1.6 A resolution.
Related PDB 2cua
Related UniProtKB P98052
[7]
Resource
Comments
Medline ID
PubMed ID 11152118
Journal Protein Sci
Year 2000
Volume 9
Pages 2068-73
Authors Soulimane T, Than ME, Dewor M, Huber R, Buse G
Title Primary structure of a novel subunit in ba3-cytochrome oxidase from Thermus thermophilus.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS)
Medline ID 20237613
PubMed ID 10775261
Journal EMBO J
Year 2000
Volume 19
Pages 1766-76
Authors Soulimane T, Buse G, Bourenkov GP, Bartunik HD, Huber R, Than ME
Title Structure and mechanism of the aberrant ba(3)-cytochrome c oxidase from thermus thermophilus.
Related PDB 1ehk
Related UniProtKB P98052 P82543
[9]
Resource
Comments
Medline ID
PubMed ID 11716725
Journal J Am Chem Soc
Year 2001
Volume 123
Pages 11678-85
Authors Fernandez CO, Cricco JA, Slutter CE, Richards JH, Gray HB, Vila AJ
Title Axial ligand modulation of the electronic structures of binuclear copper sites: analysis of paramagnetic 1H NMR spectra of Met160Gln Cu(A).
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 15735345
Journal Acta Crystallogr D Biol Crystallogr
Year 2005
Volume 61
Pages 340-3
Authors Hunsicker-Wang LM, Pacoma RL, Chen Y, Fee JA, Stout CD
Title A novel cryoprotection scheme for enhancing the diffraction of crystals of recombinant cytochrome ba3 oxidase from Thermus thermophilus.
Related PDB 1xme
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 16554303
Journal J Biol Chem
Year 2006
Volume 281
Pages 14503-13
Authors Muresanu L, Pristovsek P, Lohr F, Maneg O, Mukrasch MD, Ruterjans H, Ludwig B, Lucke C
Title The electron transfer complex between cytochrome c552 and the CuA domain of the Thermus thermophilus ba3 oxidase. A combined NMR and computational approach.
Related PDB 2fwl
Related UniProtKB

Comments
Although this enzyme is partially homologous to that from P. denitrificans (Bacteria) (M00062 in EzCatDB), the subunit/domain compositions seem to be slightly different from the counterpart enzyme.
Bacterial enzymes are composed of 3 or 4 subunits. Subunits I and II form the functional core of the enzyme complex. The subunit I binds a copper ion (CuB), two heme groups (heme A and heme A3). The subunit II binds a binuclear copper ion pair, CuA. Heme A3 and CuB form a binuclear centre for O2 reduction.
Taken together, this enzyme catalyzes the following reactions, electron transfers and dioxygen reduction, coupling with proton pumping.
4 cyt c(red) + 8 H+(in) + O2 = 4 cyt c(ox) + 2 H2O + 4 H+(out)
This enzyme catalyzes the following reactions:
(A) Electron transfer from ba3-cytochrome c (substrate;ferrocytochrome c) to CuA (subunit II):
(B) Electron transfer from CuA (subunit II) to heme A (subunit I):
(C) Electron transfer from heme A (subunit I) to binculear center (heme A3 & CuB) (subunit I):
(D) Electron transfer from CuA (subunit II) directly to CuB (subunit I):
(E) Reduction of dioxygen (O2) to H2O (at the binuclear center):
(F) Proton pump:
According to the literature [8] and [11], the following reaction proceeds as follows:
(A) Electron transfer from cytochrome c (substrate;ferrocytochrome c) to CuA (subunit II):
(A1) Indirect transfer through mainchain atoms of Ala87 and Phe88 (subunit II) to Met160 bound to CuA-1 (see [11]).
(B) Electron transfer from CuA (subunit II) to heme A (subunit I):
(B1) Indirect transfer through His157 (subunit II), mainchain carbonyl oxygen of Arg449 and mainchain amide of Arg450 (subunit I), and propionate (carboxylate) group of heme A (see M00062).
(C) Electron transfer from heme A (subunit I) to binculear center (heme A3 & CuB) (subunit I):
(C1) Indirect transfer through His386 bound to heme A iron, mainchain of Phe385, and His384 bound to heme A3 iron (see M00062).
On the other hand, the literature [8] proposed an additional electron pathway between CuA (subunit II) and CuB (subunit I).
(D) Electron transfer from CuA (subunit II) directly to CuB (subunit I):
(D1) Indirect transfer through Gln151 bound to CuA (subunit I), via Tyr136 and Trp229, and His283 bound to CuB (subunit I) (see [8]).

Created Updated
2004-03-24 2009-02-26