Figure 3, Figure 7, Figure 8, Figure 10, p.15335-15337
Figure 4, Figure 5, Figure 6, Figure 13, Figure 16, Figure 18
There are several types of urease enzymes based on the composition of subunits. This enzyme is composed of two subunits, one of which has a catalytic domain. According to the literature, at least three catalytic mechanisms have been reported. Two mechanisms for hydrolysis, which proceeds through a tetrahedral intermediate (diaminohydroxymethanolate) that gives finally carbamate and ammonia (see [12], [17] and [20]). One mechanism for elimination, which proceeds through an intermediate, cyanic acid (see [23] and [28]). (i) Hydrolysis by a reverse protonation mechanism: Carbonyl oxygen of urea is bound to Nickel-1, whereas a hydrolytic water is bound to Nickel-2. The hydrolytic water makes a nucleophilic attack on the carbonyl carbon of urea, forming a tetrahedral intermediate (diaminohydroxymethanolate). His322 (PDB;1e9y) acts as a general acid to protonate a leaving amino group, although the residue has a low pKa. Thus, carbamate and an ammonia can be produced. (see [12], [14], [19] and [20]) (ii) Hydrolysis by nucleophilic attack of a bridging hydroxide: Carbonyl oxygen of urea is bound to Nickel-1, whereas an amine group is bound to Nickel-2. The bridging hydroxide between the two nickel ions acts as a nucleophile, which attacks on the carbonyl carbon, forming a tetrahedral intermediate. The Asp residue, which is bound to Nickel-2, transfers proton from the hydroxyl group of the intermediate to the leaving amine group. His322 may stabilize the intermediate, rather than acting as a general acid. (see [17], [24], [33] and [40]) (iii) Elimination through cyanic acid (see [23], [28], [35], [36] and [37]) Alghough these reported mechanisms lead to a debate, the hydrolysis mechanism by bridging hydroxide seems to be the most reasonable, from structural viewpoints.
Urea cycle and metabolism of amino groups
Site-directed mutagenesis of the active site cysteine in Klebsiella aerogenes urease.
Structures of Cys319 variants and acetohydroxamate-inhibited Klebsiella aerogenes urease.
An evolutionary treasure: unification of a broad set of amidohydrolases related to urease.
70 Years of Crystalline Urease:? What Have We Learned?
Crystallization and preliminary high-resolution X-ray diffraction analysis of native and beta-mercaptoethanol-inhibited urease from Bacillus pasteurii.
Chemical rescue of Klebsiella aerogenes urease variants lacking the carbamylated-lysine nickel ligand.
The complex of Bacillus pasteurii urease with beta-mercaptoethanol from X-ray data at 1.65-angstrom resolution.
Characterization of metal-substituted Klebsiella aerogenes urease.
A new proposal for urease mechanism based on the crystal structures of the native and inhibited enzyme from Bacillus pasteurii: why urea hydrolysis costs two nickels.
Fluoride inhibition of Klebsiella aerogenes urease: mechanistic implications of a pseudo-uncompetitive, slow-binding inhibitor.
Preliminary crystallographic studies of urease from jack bean and from Klebsiella aerogenes.
Kinetic and structural characterization of urease active site variants.
X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), AND MUTAGENESIS OF HIS-219; ASP-221; HIS-320 AND ARG-336.
The complex of Bacillus pasteurii urease with acetohydroxamate anion from X-ray data at 1.55 A resolution.
Molecular mechanics evaluation of the proposed mechanisms for the degradation of urea by urease.
Structure-based rationalization of urease inhibition by phosphate: novel insights into the enzyme mechanism.
Structure-based computational study of the catalytic and inhibition mechanisms of urease.
Helicobacter pylori springs another surprise.
Supramolecular assembly and acid resistance of Helicobacter pylori urease.
X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS), AND SUBUNIT STRUCTURE.
Decomposition of alkyl-substituted urea molecules at a hydroxide-bridged dinickel center.
Crystallization and preliminary X-ray structure determination of jack bean urease with a bound antibody fragment.
Site-directed mutagenesis of Klebsiella aerogenes urease: identification of histidine residues that appear to function in nickel ligation, substrate binding, and catalysis.
Three-dimensional quantitative structure-activity relationship and comparative molecular field analysis of dipeptide hydroxamic acid Helicobacter pylori urease inhibitors.
Ureases: quantum chemical calculations on cluster models.
Molecular details of urease inhibition by boric acid: insights into the catalytic mechanism.
The hydrolysis of urea and the proficiency of urease.
Enzymatic catalysis of urea decomposition: elimination or hydrolysis?
Catalyzed decomposition of urea. Molecular dynamics simulations of the binding of urea to urease.
Competitive hydrolytic and elimination mechanisms in the urease catalyzed decomposition of urea.
Crystal structure of the first plant urease from jack bean: 83 years of journey from its first crystal to molecular structure.
Iron-containing urease in a pathogenic bacterium.
Chemistry of Ni2+ in urease: sensing, trafficking, and catalysis.
Urease activity in the crystalline state.
The crystal structure of urease from Klebsiella aerogenes.
At last--the crystal structure of urease.
Structures of the Klebsiella aerogenes urease apoenzyme and two active-site mutants.
Characterization of the mononickel metallocenter in H134A mutant urease.
Interaction of Urea with a Hydroxide-Bridged Dinuclear Nickel Center:? An Alternative Model for the Mechanism of Urease.
Interallelic complementation at the ubiquitous urease coding locus of soybean.