Heme-copper oxygen reductases (HCOs) are membrane bound enzymes that catalyze the complete reduction of O2 to water coupled to the translocation of up to four protons across the membrane. These enzymes contribute to the establishment and maintance of the difference of electrochemical potential across the membrane by:

  1. Charge separation, protons and electrons needed for the reaction are uptaken from different sides of the membrane, i.e. the enzymes are electrogenic;
  2. and proton translocation, part of the energy released from the catalytic reaction is used to translocate protons against a membrane potential.

The catalytic subunit of these enzymes is characterized by the presence of a low-spin heme, a binuclear center composed of a high-spin heme and a copper ion (CuB) and a tyrosine residue cross-linked to one of histidine ligand of CuB. Based on the fingerprints of their proton conducting channels they were proposed to be divided into three different types: A (further divided in A1 and A2), B and C Type enzymes (1).

Table 1 – Structural and functional properties of HCOs and NORs.
 

Binuclear center

Energy conservation

Enzyme Type

Heme-Cu

Heme-Fe

Tyr-I

Tyr-II

Charge separation

H+ translocation

D-channela

K-channelb

A

+

-

+

-

+

+

+

B

+

-

+

-

+

-

Alternative

C*

+

-

-

+

+

-

Alternative

NOR

-

+

-

-

-

-

-

* C Type HCOs are only present in Bacteria

a The amino acid residues that compose the D-channel are Asp124 , Asn199, Asn113, Asn131, Tyr35, Ser134, Ser193 and Glu278 for A1 type enzymes (P. denitrificans numbering). In the D-channel of A2 Type enzymes a tyrosine replaces the glutamate residue (1).

b K-channel of A Type enzymes is constituted by Lys354, Thr351, Ser291 and Tyr280 (Tyr-I) residues. In the alternative K-channel of B Type enzymes besides Tyr-I, those residues are replaced by a Thr, a Ser and a Tyr residues. The alternative K-channel from C Type enzymes is constituted by Tyr-II and a Ser and a Tyr residue in the same sequence position of the Thr-351 and SerI-291 residues (1).


Nitric oxide reductases (NORs) are membrane bound enzymes that catalyze the reduction of NO to water and N2O. Their catalytic subunit harbors a low spin heme and a binuclear center composed of a high-spin heme and an iron ion (Fe) (2). NORs do not pump protons and are non-electrogenic since protons and electrons needed for the catalytic reaction are uptaken from the same side of the membrane. Despite these differences, their catalytic subunit share with HCOs the same predicted structural fold, and the same SCOP family classification, thus NORs are proposed to have shared a common ancestor with HCOs (3).


This database consists of a compilation of HCO and NOR sequences as well as their available annotations retrieved from several commonly used databases (4-9). Moreover it allows an automated classification of any HCO or NOR given sequence according to their type.


References

  1. Pereira, M.M., M. Santana, and M. Teixeira, A novel scenario for the evolution of haem-copper oxygen reductases, Biochim Biophys Acta, 2001. 1505(2-3), 185-208.
  2. Zumft, W.G., Nitric oxide reductases of prokaryotes with emphasis on the respiratory, heme-copper oxidase type, J Inorg Biochem, 2005. 99(1), 194-215.
  3. Murzin, A.G., et al., SCOP: a structural classification of proteins database for the investigation of sequences and structures, J Mol Biol, 1995. 247(4), 536-40.
  4. Gough, J., et al., Assignment of homology to genome sequences using a library of hidden Markov models that represent all proteins of known structure, J Mol Biol, 2001. 313(4), 903-19.
  5. Finn, R.D., et al., The Pfam protein families database, Nucleic Acids Research, 2008. 36, D281-D88.
  6. Gasteiger, E., et al., ExPASy: the proteomics server for in-depth protein knowledge and analysis, Nucleic Acids Research, 2003. 31(13), 3784-88.
  7. Kanehisa, M., et al., From genomics to chemical genomics: new developments in KEGG, Nucleic Acids Research, 2006. 34, D354-D57.
  8. Pruitt, K.D., T. Tatusova, and D.R. Maglott, NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins, Nucleic Acids Research, 2007. 35, D61-D65.
  9. Sigrist, C.J., et al., PROSITE, a protein domain database for functional characterization and annotation, Nucleic Acids Res. 38(Database issue), D161-6.