Enzyme

1.15.1.1 - Superoxide dismutase

Alternative Name(s)

There are no alternative names for this Enzyme

Catalytic Activity

2 H(+) + 2 superoxide = H2O2 + O2

Cofactors

Fe cation or Mn(2+) or (Zn(2+) and Cu cation).

Reaction Mechanism

    superoxide dismutase By Reference

    Copper-zinc superoxide dimutase (CuZnSOD) catalyses the disproportionation of superoxide into dioxygen and hydrogen peroxide.

    In higher organisms, superoxide anions are produced as an occasional byproduct during the one-electron reduction of dioxygen in respiration and photosynthesis. Superoxides are also produced by macrophages as a part of the immune response. Excess amounts of superoxides can inactivate enzymes with iron-sulphur clusters and can lead to the formation of highly oxidising species that can damage cellular constituents. Therefore, organisms must have ways to regulate the concentration of superoxide concentrations. Many Gram-negative bacterial pathogens also possess CuZnSOD to counteract the phagocyte superoxide burst from their hosts.

    Based on crystal structures, a mechanism is proposed. Guided by the electrostatic channel, superoxide enters the active site, displaces a water molecule, forms a hydrogen bond with Arg143 and binds to the copper(II) ion. Bound superoxide reduces Cu(II) to Cu(I) with simultaneous breaking of the bond between His63 and the Cu(I) ion. Dioxygen is released and His63 is protonated by the solvent. Another superoxide enters the active site. Electron is transferred from Cu(I) to the superoxide and at the same time, two protons are transferred to the superoxides from protonated His63 and a water molecule, forming hydrogen peroxide. Cu(II) then moves to reform the histidine bridge.

    Zn(II) bound to His63 ND1 raises the pKa of NE2 to ~13, so that unliganded NE2 will always be protonated at physiological pH.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    His P00445 72 2jcw 71
    Asp P00445 84 2jcw 83
    His P00445 81 2jcw 80
    His P00445 121 2jcw 120
    His P00445 64 2jcw 63
    Arg P00445 144 2jcw 143
    His P00445 47 2jcw 46
    His P00445 49 2jcw 48
    Step Components

    native state of enzyme regenerated, coordination to a metal ion, native state of cofactor regenerated, radical termination, cofactor used, proton relay, electron transfer, proton transfer

    Step 1.

    In the resting state of the enzyme, there is a water coordinated to the copper, analogous to the final state of this step, save that the histidine in the resting state is negatively charged and bound to the copper II ion. The superoxide gives up its electron to the Copper II ion. Dioxygen, no longer charged and electrostatically attracted to Arg143, diffuses out of the active site channel, and it is replaced by a water molecule, which starts of as a oxonium and concurrently gives up its proton to the His63, which breaks the histidine bridge [PMID:10026301

    Step 2.

    The second superoxide molecule enters the active site cavity, displaces a water molecule and hydrogen bonds with the protonated NE2 atom of His63 and a water molecule. A chain of water molecules can relay protons to the active site, replenishing those delivered to form peroxide. The neutral hydrogen peroxide is displaced from the active site by a water molecule to return the enzyme to its initial resting state

    Products.

    The products of the reaction.

Reaction Parameters

  • Kinetic Parameters
    Organism KM Value [mM] Substrate Comment
    Solanum lycopersicum 0.0016 riboflavin
    Psidium guajava 2.3 riboflavin
    Bos taurus 0.355 O2-
    Avicennia marina 0.0115 superoxide pH 8.2, 22°C
  • Temperature
    Organism Temperature Range Comment
    Stemona tuberosa 0 - 50 activity range
    Pseudoalteromonas sp. ANT506 0 - 50 activity range, 13.9% of maximal activity at 0°C, 25.7% at 10°C
    Curcuma aromatica 0 - 80 activity range between -10-80°C
    Caragana jubata 0 - 80 activity range between -10-80°C
    Ulva linza 0 - 35 maximal enzyme activity at 35°C, and 29.8% relative activity at 0°C
  • pH
    Organism pH Range Comment
    Rhodotorula mucilaginosa 1 - 11 activity range, 75% of maximal activity at pH 1.0, 45% at pH 11.0, profile overview
    Cristaria plicata 2 - 9 activity range, the enzyme shows 30% of maximal activity at pH 10.0 and is inactive at pH 11.0
    Danio rerio 2.2 - 11.2 high enzyme activity
    Stemona tuberosa 3 - 10 70% of maximal activity within this range
    Sonneratia alba 3 - 7 high activity range

Associated Proteins

Protein name Organism
Superoxide dismutase [Fe] 2, chloroplastic Mouse-ear cress
Superoxide dismutase [Cu-Zn] A African clawed frog
Superoxide dismutase [Cu-Zn] B African clawed frog
Superoxide dismutase [Fe-Zn] Streptomyces griseus
Cell surface superoxide dismutase [Cu-Zn] 6 Yeast

Citations