Theoretical Study of Intermediates in the Urate Oxidase Reaction

Kahn, Kalju

doi:10.1006/bioo.1999.1142

Cited by 19 publications

(11 citation statements)

References 42 publications

(51 reference statements)

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“…Although allantoin appears to be the ultimate product of urate oxidase action upon urate, absorption spectroscopy and nuclear magnetic resonance (NMR) studles suggest that the enzyme catalyzes the conversion of urate to a metastable species which decays nonenzymatically to allantoin [19,20]; this species appears to be 5-hydroxyisourate, as shown in elegant studies of Kahn and Tipton [21,22].…”

Section: Introductionmentioning

confidence: 99%

Identification and structural characterization of a transient radical species in the uricase reaction mechanism

et al. 2007

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Uricase catalyzes the oxidation of urate to form allantoin, carbon dioxide and hydrogen peroxide. In this article, we demonstrate for the first time the presence of a radical intermediate involved in the reaction mechanism. Such radical species was entrapped using 5-diethoxyphosphoryl-5-methyl-l-pyrroline N-oxide as spin trap and the relative adduct was detected by electron paramagnetic resonance (EPR) technique. A structure of such radical (5-hydroperoxy isourate) is proposed, through chemical results and density functional theory calculations of the EPR coupling constants.

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Section: Introductionmentioning

confidence: 99%

Identification and structural characterization of a transient radical species in the uricase reaction mechanism

et al. 2007

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“…In solution, 5-HIU evolves spontaneously to a racemic mixture of allantoin, while in vivo it is rapidly degraded to (+)-allantoin by a separate enzyme system. [15] b) Peroxide-dependent[2d, 16] (path A) and peroxide-independent[5] (path B) mechanistic proposals. The shaded green area emphasizes the solvent network surrounding the five-membered ring.…”

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confidence: 99%

Direct Evidence for a Peroxide Intermediate and a Reactive Enzyme–Substrate–Dioxygen Configuration in a Cofactor‐free Oxidase

et al. 2014

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Cofactor-free oxidases and oxygenases promote and control the reactivity of O2 with limited chemical tools at their disposal. Their mechanism of action is not completely understood and structural information is not available for any of the reaction intermediates. Near-atomic resolution crystallography supported by in crystallo Raman spectroscopy and QM/MM calculations showed unambiguously that the archetypical cofactor-free uricase catalyzes uric acid degradation via a C5(S)-(hydro)peroxide intermediate. Low X-ray doses break specifically the intermediate C5=OO(H) bond at 100 K, thus releasing O2 in situ, which is trapped above the substrate radical. The dose-dependent rate of bond rupture followed by combined crystallographic and Raman analysis indicates that ionizing radiation kick-starts both peroxide decomposition and its regeneration. Peroxidation can be explained by a mechanism in which the substrate radical recombines with superoxide transiently produced in the active site.

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“…The semi empirical models MNDO, AM1, and PM3 are often used in computational chemistry because they allow study of systems that are out of reach of more accura te methods. For example, modern semi-empirical programs allow study of molecules consisting of thousands of atoms while ab initio calculations that produce similar thermochemical accuracy are feasible on molecules consisting of less than 50-70 atoms (Young, 2002;Kahn and Bruice, 2000;Kahn and Tipton, 2000;Kahn, 1999;Stewart, 2007). Only the most suitable calculation results of the semi empirical method (PM3) were reported in this study (Castells et al, 1980;Jordan, 1976;Shin et al, 1993;Shaffer and Wierschke, 1993;Burling and Goldstein, 1992;Kabir and Sapse, 1991;Mari et al, 1992).…”

Section: Introductionmentioning

confidence: 84%

DFT and PM3 Computational Studies of the Reaction Mechanism of the Oxidation of L-Tyrosine by Iodine in the Gas Phase

Shallangwa

Uzairu

Ajibola

et al. 2014

Aceh Int. J. Sci. Technol

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The oxidation of L-Tyrosine by molecular iodine was studied using semi-empirical and density functional theory methods. Molecular information such as net charges, values of frontier orbital energies, composition, proportions and bonding contribution were obtained and analyzed. Thus, possible reactive sites were proposed and the reaction mechanism was postulated. The postulated transition states, intermediates and products were also computed using the PM3 and DFT methods. Computed enthalpies of the oxidation reaction at standard conditions for the PM3 and DFT calculation were 216.97 kJ/mol and -36327404.72 kJ/mol respectively. The calculated ΔG o and ΔS o , for the transition states according to the DFT model were both large and negative indicating that the processes were exergonic associative substitution reactions.

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Theoretical Study of Intermediates in the Urate Oxidase Reaction

Cited by 19 publications

References 42 publications

Identification and structural characterization of a transient radical species in the uricase reaction mechanism

Identification and structural characterization of a transient radical species in the uricase reaction mechanism

Direct Evidence for a Peroxide Intermediate and a Reactive Enzyme–Substrate–Dioxygen Configuration in a Cofactor‐free Oxidase

DFT and PM3 Computational Studies of the Reaction Mechanism of the Oxidation of L-Tyrosine by Iodine in the Gas Phase

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