Nickel urease

Colpas GJ, Brayman TG, Ming L-J, Hausinger RP. 1999. Identification of metalbinding residues in the Klebsiella aerogenes urease nickel metallochaperone, UreE. Biochemistry 38 4078-88. 

Until the discovery in 1975 of nickel in jack bean urease (which, 50 years previously, had been the first enzyme to be isolated in crystalline form and was thought to be metal-free) no biological role for nickel was known. Ureases occur in a wide variety of bacteria and plants, catalyzing the hydrolysis of urea,... 

Results from an array of methods, including X-ray absorption, EXAFS, esr and magnetic circular dichroism, suggest that in all ureases the active sites are a pair of Ni" atoms. In at least one urease,these are 350 pm apart and are bridged by a carboxylate group. One nickel is attached to 2 N atoms with a fourth site probably used for binding to urea. The second nickel has a trigonal bipyramidal coordination sphere. 

In contrast to the abundance of Fe-proteins, there are only six known nickel-containing enzymes hydrogenase, CO dehydrogenase (CODA), acetyl-CoA synthase (ACS), superoxide dismutase, urease, and S-methyl-CoM methylreductase. Among these enzymes, it exists in very diverse environments, including a dinickel site (urease), a Ni-Fe heterobinuclear site (hydrogenase), a Ni-Fe4S4 heterometallic... 

Nickel exists in the tunicate Trididemnum solidum as the nickel complex of a modified chlorin (Bible et al. 1988) and is a component of a number of enzymes. Urease is the classic example of a nickel-containing enzyme, and several enzymes contain both nickel and iron. Details of enzymes that contain nickel have been provided in a review (Mulrooney and Hausinger 2003), and only brief summaries are provided ... 

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. 

Kinetic evidence obtained for intramolecular proton transfer between nickel and coordinated thiolate, in a tetrahedral complex containing the bulky triphos ligand (Pl PCE CE PPh to prevent interference from binuclear p-thiolate species, is important with respect to the mechanisms of action of a number of metalloenzymes, of nickel (cf. urease, Section VII. B.4) and of other metals (289). 

Hydrogenases are not the only nickel-containing enzyme, and researchers must therefore compare the maturation of different nickel proteins to obtain an integrated picture of nickel metabolism. Indeed, similarities between some of the hydrogenase-related nickel-processing proteins with urease and carbon monoxide dehydrogenase maturation factors have been noted, and this has facilitated interpretations of the results for... 

Table 6.3. Effect of nickel supplementation on hydrogenase and urease activities.

Nickel-Dependent Hydrogenase Expression 79 Immunoblot of Urease Large Subunit Cells Grown Without Nickel Supplementation Wt hypA... 

Figure 6.5. Immunoblot of the urease large subunit. Extracts of H. pylori wild type (WT) and a hypA mutant from cells grown without nickel supplementation were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and identified by blotting with an anti-urease large-subunit antiserum. Urease activity was 58pmolmin mg for the wild type and Opmolmin" mg for the hypA mutant.

Mobley HLT, Garner RM, Bauerfeind R 1995. Helicobacter pylori nickel-transport gene AA synthesis of catalytically active urease in Escherichia coli independent of growth conditions. Mol Microbiol 16 97-109. 

Olson JW, Mehta NS, Maier RJ. 2001. Requirement of nickel metabohsm proteins HypA and HypB for full activity of both hydrogenase and urease in Helicobacter pylori. Mol Microbiol 39 176-182. 

Urease is a very unusual enzyme in the sense that it contains an atom of nickel that is required for activity. Many enzymes contain metal ions but very few have nickel as that metal. Incidentally, urease is not an easy enzyme to crystaUize. I tried it as a graduate student many years ago and developed high regard for the skills of James Sumner. 

Urease [EC 3.5.1.5], a protein containing two tightly bound nickel ions, catalyzes the hydrolysis of urea. Technically, the enzymatic phase proceeds up to the formation of carbamate ... 

The high specificity of siderophore iron coordination has been extensively explored in iron-chelation therapy for various medical applications, including iron overload diseases, control of iron in specific brain tissues , arresting the growth and proliferation of malaria parasite within their host , as well as arresting the proliferation of cancer cells . Other directions for metal ligation involve enzyme inhibition, which have been demonstrated by the inhibition of urease by coordination of hydroxamate ligand to nickel ions and zinc coordination in matrix metalloprotease (MMP) inhibition by primary hydroxamates. ... 

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