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Urease models

A number of dinickel urease models with urea bound to the dinickel center imphcate preferential binding of urea via the carbonyl oxygen atom " this coordination mode is... [Pg.2897]

Since a number of years we work on urease models based on synthetic receptors. Metallomacrocycles with binaphtyl moieties incorporated give the possibilty to introduce functional groups at the 3- and 3 -postion. The synthesis of 16 and 17 has been carried out according to the strategy described above [ref 18]. [Pg.337]

Ligand and complex design in biomimetic systems is diverse but a few general concepts are normally followed (i) the metal ions employed are often the same as in the native systems e.g. Ni(II) in urease models [68] and (ii) pyridine or pyrazole residues are often used to mimic the histidine residues in the enzymes phenol, carboxylate, pyrazolate or water molecules serve as mimics for bridging residues like aspartate, lysine or water/hydroxide and (iii) dinucleating ligands are used to bring the two metal ions into close proximity. [Pg.8]

The dinuclear active site of urease (1) has been studied in great detail23-29 and has inspired manifold model studies—hence a separate section, Section 6.3.4.12.7, is dedicated to the coordination chemistry related to urease. E. coli Glx I is the first example of a Ni-dependent isomerase and contains a single Ni11 ion coordinated by two histidines, two axial carboxylates of glutamic acid, and two water molecules (2).30-32 It is not active with Zn bound, which is believed to result from the inability of the Zn-substituted enzyme to bind a second aqua ligand and to adopt a six-coordinate structure. [Pg.249]

Biomimetic chemistry of nickel was extensively reviewed.1847,1848 Elaborate complexes have been developed in order to model structural and spectroscopic properties as well as the catalytic function of the biological sites. Biomimetic systems for urease are described in Section 6.3.4.12.7, and model systems for [Ni,Fe]-hydrogenases are collected in Section 6.3.4.12.5. [Pg.421]

Type (820) dinickel complexes offer the opportunity of substrate binding within the bimetallic pocket, and highly preorganized complexes of this type have also been employed as model systems for the urease metalloenzyme (see Section 6.3.4.12.7). The Ni—Ni separation in type (820) complexes can be... [Pg.449]

The results of most model studies for Ni-mediated urea degradation reported to date are consistent with a cyanate intermediate. While this differs from the most likely mechanism of urease activity as deduced from protein crystallography, there is still no definitive evidence ruling out a transient Ni-bound cyanate intermediate for the enzyme. [Pg.461]

A model enzyme (protein), urease, did not lose much of its activity until the eompaetion pressure exeeeded 474 mPa (63 mm Hg) above which 50% of the relative aetivity was lost [95],... [Pg.213]

Fig. 2. Ni K-edge EXAFS spectrum of urease. The curve (+) is calculated for a single type of nickel site, and the minimization of parameters was based on those for the model complexes Ni(l-n-propyl-2-hydroxybenzylbenzimidazole)3(Cl04) and Ni(2-hydroxy-methylbenzimidazole)3Br2. Atoms (with distances in nanometers given in parentheses) in the simulation were N (0.204), O (0.206), O (0.225), C (0.294), C (0.312), N (0.392), and C (0.394). Reproduced, with permission, from Ref. 34. Fig. 2. Ni K-edge EXAFS spectrum of urease. The curve (+) is calculated for a single type of nickel site, and the minimization of parameters was based on those for the model complexes Ni(l-n-propyl-2-hydroxybenzylbenzimidazole)3(Cl04) and Ni(2-hydroxy-methylbenzimidazole)3Br2. Atoms (with distances in nanometers given in parentheses) in the simulation were N (0.204), O (0.206), O (0.225), C (0.294), C (0.312), N (0.392), and C (0.394). Reproduced, with permission, from Ref. 34.
The enzyme urease catalyzes the hydrolysis of urea to form carbamate ion (equation 32). At pH 7.0 and 38 °C, the urease-catalyzed hydrolysis of urea is at least 1014 times as fast as the spontaneous hydrolysis of urea. Jack bean urease is a nickel(II) metalloenzyme502 with each of its six identical subunits containing one active site and two metal ions, and at least one of these nickel ions is implicated in the hydrolysis. It has been suggested503 that all substrates for urease (urea, N-hydroxyurea, 7V-methylurea, semicarbazide formamide and acetamide) are activated towards nucleophilic attack on carbon as a result of O-coordination to the active nickel(II) site as in (155). Nickel(II) ions have been found504 to promote the ethanolysis and hydrolysis of N-(2-pyridylmethyl)urea (Scheme 39) and this system is considered to be a useful model for the enzyme. [Pg.470]

Comparison of blood serum samples analysis data, obtained with the use of urease-containing and proposed enzyme free sensors shows that the results are similar (Table 39.1). It confirms that using anion-exchange column provides good separation of the interfering compounds and analyte. Moreover it is worth taking into account that real samples contain compounds mentioned in Section 39.5 in lower concentrations than in the model solution. [Pg.1216]

Figure 1 Model of the structure of the active site of urease, after Jabri et al. [27], and reaction cycle. (After Refs. 21,161.)... Figure 1 Model of the structure of the active site of urease, after Jabri et al. [27], and reaction cycle. (After Refs. 21,161.)...
Biophysical studies of the urease metal centre in the presence and absence of inhibitors, in conjunction with kinetic data provide the model of the bi-Ni site shown in 1. Certain inhibitors are thought to bridge the two nickel atoms consistent with a bridged transition state during urea hydrolysis. The ligands for nickel are believed not to contain sulphur, however, an essential cysteine is proximal to the active site. Comparisons of diethylpyrocarbonate reactivity for apo- and halo-enzyme are consistent with His as a ligand to nickel (Lee et al., 1990). [Pg.114]

Urea-Urease Modulated System. This system was developed several years ago as a model for testing the feasibility of this concept. Because it has been described previously (2), it will only be summarized here. [Pg.173]

Recently, Wada et al. (1999) have demonstrated that a daily oral dose of 10 mg of bovine LF for 3-4 weeks to H. pylori-infected mice significantly decreased the number of this bacterium colonising in the stomach. The authors suggested that the glycans present in LF may bind to the bacterial adhesins, thus interfering with the attachment of H. pylori to the epithelial cells. These findings are supported by another mouse model study (Dial et al., 1998), which showed that oral administration of 4 mg of bovine LF per day for 3 weeks reduces gastric urease activity and H. pylori colonisation in the stomach. [Pg.187]

Metalloenzymes pose a particular problem to both experimentalists and modelers. Crystal structures of metalloenzymes typically reveal only one state of the active site and the state obtained frequently depends on the crystallization conditions. In some cases, states probably not relevant to any aspect of the mechanism have been obtained, and in many cases it may not be possible to obtain states of interest, simply because they are too reactive. This is where molecular modeling can make a unique contribution and a recent study of urease provides a good example of what can be achieved119 1. A molecular mechanics study of urease as crystallized revealed that a water molecule was probably missing from the refined crystal structure. A conformational search of the active site geometry with the natural substrate, urea, bound led to the determination of a consensus binding model[I91]. Clearly, the urea complex cannot be crystallized because of the rate at which the urea is broken down to ammonia and, therefore, modeling approaches such as this represent a real contribution to the study of metalloenzymes. [Pg.164]

IV. MODELS OF THE INHIBITED UREASE ACTIVE SITE V. FUTURE PERSPECTIVES... [Pg.487]

Historically, the first chemical synthesis of urea by Wohler, from ammonium cyanate in 1828, was a milestone that established a bridge between inorganic and organic chemistry. Urease was the first enzyme ever to be crystallized (6), and it was the first protein shown to contain nickel ions in the active site (7). The first X-ray crystal structure of urease became known in 1995 (8). Significant progress was made since then toward an understanding of its catalytic mechanism, as well as toward the structural and functional emulation of its active site by synthetic model complexes (5, 9). [Pg.488]

An alternative scenario was put forward based on the crystal structures of urease inhibited by either phosphate, diamidophosphate, or borate (4,5, 28). It gets some support from the kinetic findings for fluoride inhibition of urease (29), as well as from recent model calculations (30, 31). Boric acid, known to be a competitive inhibitor of urease, can be considered a good substrate analogue, since it is isoelectronic with urea and has the same shape and dimension. Bacillus pasteurii could be crystallized in the presence of boric acid. The structure reveals that a molecule of B(OH)3 is symmetrically spanning the nickel ions, replacing Wj, W2,... [Pg.490]


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