Inhibition of Urease by Hydroquinones: A Structural and Kinetic Study

Abstract

Hydroquinones are a class of organic compounds abundant in nature that result from the full reduction of the corresponding quinones. Quinones are known to efficiently inhibit urease, a Ni II -containing enzyme that catalyzes the hydrolysis of urea to yield ammonia and carbonate and acts as a virulence factor of several human pathogens, in addition to decreasing the efficiency of soil organic nitrogen fertilization. Here, we report the molecular characterization of the inhibition of urease from Sporosarcina pasteurii (SPU) and Canavalia ensiformis (jack bean, JBU) by 1,4-hydroquinone (HQ) and its methyl and tert-butyl derivatives. The 1.63-Å resolution X-ray crystal structure of the SPU-HQ complex discloses that HQ covalently binds to the thiol group of αCys322, a key residue located on a mobile protein flap directly involved in the catalytic mechanism. Inhibition kinetic data obtained for the three compounds on JBU reveals the occurrence of an irreversible inactivation process that involves a radical-based autocatalytic mechanism.

Fabrication of multinuclear copper cluster-based coordination polymers as urease inhibitors

“…24,25 Cu-CPs, as a type of candidate UI, may not only inhibit the activation process of urease deacylated protein, but also fill the active pocket of urease well, establish interactions between the active sites of urease, occupy the binding sites that should belong to nickel, causing irreversible inhibition of urease activity, and then block the path of urea into the active site to achieve the effect of urease inhibition. 26 Incorporating the created Cu-CPs into fertilizers may minimize nitrogen fertilizer hydrolysis, reduce ammonia volatilization, and increase nitrogen fertilizer usage. 27 Herein, two copper cluster-based CPs (Cu-CPs) were successfully prepared, [Cu 2 (4-…”

Is bismuth(iii) able to inhibit the activity of urease? Puzzling results in the quest for soluble urease complexes for agrochemical and medicinal applications

“…35 The quest for novel urease inhibitors is thus central to various fields 36,37 and several compounds have been found to inhibit urease. 7,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] Another strategy to inhibit urease is the use of coordination polymers (CPs) and complexes, 57,58 formed by the self-assembly of metal ions and organic ligands and representing one of the most prolific research areas of crystal engineering and medicinal inorganic chemistry in the last 15 years. Interest in such compounds comes from their double organic-inorganic nature and the possibility of simultaneously exhibiting the properties of both classes.…”

Water-Soluble Pyrolysis Products as Novel Urease Inhibitors Safe for Plants and Soil Fauna

“…These compounds have a structural analogy with urea and are capable of temporarily blocking soil ureases by binding to the Ni­(II) ions in the active site of the enzyme, decreasing the urea hydrolysis rate. Other inhibitors containing a phenolic scaffold, such as catechol and its mono- and dimethyl derivatives and hydroquinones, have been proven to inhibit urease by binding to a conserved cysteine residue located onto a mobile helix-turn-helix motif in the active site cavity. − Catechol, in particular, is one of the simplest molecules bearing a phenolic structure identified as a powerful inhibitor of soil urease, capable of inhibiting more than 70% of the activity even at low concentrations . Even if several phenolic compounds have marked inhibitory effects on urease activity in the soil, other natural macrostructures containing many phenolic moieties like lignin, tannins, and humic acids seem not to behave likewise, presumably because of their lower water solubility than single phenolic units .…”