Enzyme - Urease

Alternative Name(s)

There are no alternative names for this Enzyme

Catalytic Activity

2 H(+) + H2O + urea = CO2 + 2 NH4(+)



Reaction Mechanism

    Ureases hydrolyse urea into ammonia and carbamate. Ureases have been isolated from a wide range of bacteria, fungi and higher plants where it allows the organism to use urea as a nitrogen source. Ureases uses an almost unique bi-nickel catalytic centre which is liganded by a carbamylated lysine.

    The mechanism of this enzyme has been subject to debate since the early 1920s and the precise steps in catalysis remain unclear [PMID:20471401].

    A third proposal is the elimination reaction from Barios and Lippard [PMID:11300826] has also been proposed on the observation of cyanic intermediates. Theoretical work by Estiu and Merz [PMID:16584179, PMID:17676790] suggests that the elimination pathway may occur in competition with the more traditionally proposed mechanisms.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Lys P18314 217 1fwj 217
    Asp P18314 360 1fwj 360
    His P18314 320 1fwj 320
    His P18314 134 1fwj 134
    His P18314 136 1fwj 136
    His P18314 246 1fwj 246
    His P18314 272 1fwj 272
    His P18314 219 1fwj 219
    Asp P18314 221 1fwj 221
    Arg P18314 336 1fwj 336
    Step Components

    inferred reaction step, bimolecular nucleophilic addition, intramolecular elimination, reaction occurs outside the enzyme, native state of enzyme regenerated

    Step 1.

    Asp221 deprotonates His219, which in turn abstracts a proton from the Ni(II) bound urea, forming a negatively charged intermediate.

    Step 2.

    His320 deprotonats Asp221.

    Step 3.

    The negatively charged intermediate collapses, eliminating ammoinia, which abstracts the proton from His320.

    Step 4.

    Cyanic acid is the product of this enzyme mechanism, thus it is likely that the final hydrolysis occurs outside of the active site.

    Step 5.

    Ammonia is eliminated in the final non-enzyme catalysed step of the reaction.

    Step 6.

    Inferred step to regenerate the enzyme's active site. Two water molecules displace the product to form the ground state. It is unclear how the His219 returns to it's native state, we have represented a water facilitated tautomerisation reaction here.


    The products of the reaction.

Reaction Parameters

  • Kinetic Parameters
    Organism KM Value [mM] Substrate Comment
    Klebsiella aerogenes 1250 Urea pH 7.0, 37°C
    Canavalia ensiformis 2000 Urea pH 7.0, 38°C
  • Temperature
    Organism Temperature Range Comment
    Brucella suis bv. 1 10 - 45
    Pisum sativum 10 - 80 activity range, profile overview
    Limosilactobacillus fermentum 10 - 15
    Lysinibacillus sphaericus 20 - 50 20°C: about 40% of maximal activity, 25°C: about 70% of maximal activity, 45°C: about 50% of maximal activity, 50°C: about 30% of maximal activity
    Cajanus cajan 20 - 60 20°C: about 90% of maximal activity, 60°C: about 40% of maximal activity, soluble enzyme
  • pH
    Organism pH Range Comment
    Edwardsiella ictaluri 2 - 3 optimal activity
    Enterobacter sp. 3 - 7 pH 3.0: about 65% of maximal activity, pH 7.0: anout 75% of maximal activity
    Providencia rettgeri 3 - 8.5 activity range, recombinant enzyme, profile overview
    Yersinia enterocolitica 4 - 7
    Pisum sativum 4 - 8.5 activity range, profile overview

Associated Proteins

Protein name Organism
Urease subunit gamma 2 Psychrobacter cryohalolentis (strain K5)
Urease subunit gamma Synechococcus sp. (strain WH7805)
Urease Mouse-ear cress
Urease subunit alpha 2 Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)
Urease subunit gamma/beta Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)