Inhibition of jack bean urease by organobismuth compounds

Murafuji, Toshihiro; Azuma, Takako; Miyoshi, Youhei; Ishibashi, Motoko; Rahman, Asma; Migita, Kouto; Sugihara, Yoshikazu; Mikata, Yuji

doi:10.1016/j.bmcl.2005.12.034

Cited by 21 publications

(15 citation statements)

References 16 publications

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“…Bismuth complexes such as, RBC as well as some triarylbismuthanes can inhibit urease activity [42,43]. Inhibition of jack bean urease by the triarylbismuthanes compounds is in good agreement with observed antibacterial activity of the compounds against H. pylori [43]. Both Bi(EDTA) and Bi(Cys) 3 are competitive inhibitors of jack bean urease, while RBC is a noncompetitive inhibitor.…”

Section: Potential Protein Targets Of Bismuth Drugssupporting

confidence: 58%

“…It catalyzes the hydrolysis of urea to yield carbamate and ammonia and thus neutralizes its immediate environment of the bacterium to aid its survival under acidic conditions of the gastric lumen and mucosa. Bismuth complexes such as, RBC as well as some triarylbismuthanes can inhibit urease activity [42,43]. Inhibition of jack bean urease by the triarylbismuthanes compounds is in good agreement with observed antibacterial activity of the compounds against H. pylori [43].…”

Section: Potential Protein Targets Of Bismuth Drugssupporting

confidence: 58%

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Recent advances in bioinorganic chemistry of bismuth

Sun

2012

Current Opinion in Chemical Biology

163

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Bismuth has been used in medicine for over two centuries for the treatment of various diseases, in particular for gastrointestinal disorders, owing to its antimicrobial activity. Recent structural characterization of bismuth drugs provides an insight into assembly and pharmacokinetic pathway of the drugs. Mining potential protein targets inside the pathogen via metallomic/metalloproteomic approach and further characterization on the interactions of bismuth drugs with these targets laid foundation in understanding the mechanism of action of bismuth drugs. Such studies would be beneficial in rational design of new potential drugs.

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Section: Potential Protein Targets Of Bismuth Drugssupporting

confidence: 58%

Section: Potential Protein Targets Of Bismuth Drugssupporting

confidence: 58%

Recent advances in bioinorganic chemistry of bismuth

Sun

2012

Current Opinion in Chemical Biology

163

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“…The enzyme is widely distributed in nature and is found in a variety of plants, algae, fungi, bacteria and soil [1-3]. Thus, urease plays an important role in the nitrogen metabolism of many microorganism and plants [4,5]. Despite the great importance of urease in biotechnology and medicine and also continuous interest in many laboratories [6-11], the mechanisms of hydrolysis of the metal active site of the enzyme have not been studied in detail [12].…”

Section: Introductionmentioning

confidence: 99%

Kinetics and mechanism of jack bean urease inhibition by Hg2+

Chen

Liu

et al. 2012

Chemistry Central Journal

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BackgroundJack bean urease (EC 3.5.1.5) is a metalloenzyme, which catalyzes the hydrolysis of urea to produce ammonia and carbon dioxide. The heavy metal ions are common inhibitors to control the rate of the enzymatic urea hydrolysis, which take the Hg2+ as the representative. Hg2+ affects the enzyme activity causing loss of the biological function of the enzyme, which threatens the survival of many microorganism and plants. However, inhibitory kinetics of urease by the low concentration Hg2+ has not been explored fully. In this study, the inhibitory effect of the low concentration Hg2+ on jack bean urease was investigated in order to elucidate the mechanism of Hg2+ inhibition.ResultsAccording to the kinetic parameters for the enzyme obtained from Lineweaver–Burk plot, it is shown that the Km is equal to 4.6±0.3 mM and Vm is equal to 29.8±1.7 μmol NH3/min mg. The results show that the inhibition of jack bean urease by Hg2+ at low concentration is a reversible reaction. Equilibrium constants have been determined for Hg2+ binding with the enzyme or the enzyme-substrate complexes (Ki =0.012 μM). The results show that the Hg2+ is a noncompetitive inhibitor. In addition, the kinetics of enzyme inhibition by the low concentration Hg2+ has been studied using the kinetic method of the substrate reaction. The results suggest that the enzyme first reversibly and quickly binds Hg2+ and then undergoes a slow reversible course to inactivation. Furthermore, the rate constant of the forward reactions (k+0) is much larger than the rate constant of the reverse reactions (k-0). By combining with the fact that the enzyme activity is almost completely lost at high concentration, the enzyme is completely inactivated when the Hg2+ concentration is high enough.ConclusionsThese results suggest that Hg2+ has great impacts on the urease activity and the established inhibition kinetics model is suitable.

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“…Several reports have revealed that bismuth compounds can inhibit urease activity [116][117][118]. The metal was found to inhibit urease activity via the binding to Cys319, a cysteine at the entrance of the active site of the enzyme.…”

Section: Interaction Of Bismuth With Proteins and Enzymesmentioning

confidence: 99%