PROSITE documentation PDOC00075

Cytochrome c oxidase subunit II signature and profiles

Cytochrome c oxidase (EC 1.9.3.1) [1,2] is an oligomeric enzymatic complex which is a component of the respiratory chain and is involved in the transfer of electrons from cytochrome c to oxygen. In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane. The enzyme complex consists of 3-4 subunits (prokaryotes) to up to 13 polypeptides (mammals).

Subunit 2 (CO II) transfers the electrons from cytochrome c to the catalytic subunit 1. It contains two adjacent transmembrane regions in its N-terminus and the major part of the protein is exposed to the periplasmic or to the mitochondrial intermembrane space, respectively. CO II provides the substrate-binding site and contains a copper center called Cu(A), located in the extramembrane domain (see <PDB:1OCZ; B>), probably the primary acceptor in cytochrome c oxidase. An exception is the corresponding subunit of the cbb3-type oxidase which lacks the copper A redox-center. Several bacterial CO II have a C-terminal extension that contains a covalently bound heme c.

It has been shown [3,4] that nitrous oxide reductase (EC 1.7.99.6) (gene nosZ) of Pseudomonas has sequence similarity in its C-terminus to CO II. This enzyme is part of the bacterial respiratory system which is activated under anaerobic conditions in the presence of nitrate or nitrous oxide. NosZ is a periplasmic homodimer that contains a dinuclear copper center, probably located in a 3-dimensional fold similar to the cupredoxin-like fold that has been suggested for the copper-binding site of CO II [3].

The dinuclear purple copper center is formed by 2 histidines and 2 cysteines [5]. We used this region as a signature pattern. The conserved valine and the conserved methionine are said to be involved in stabilizing the copper-binding fold by interacting with each other. We also developed two profiles, one directed against the transmembrane region and one against the copper center.