Horseradish peroxidase. XLII. Oxidations of <scp>L</scp>-tyrosine and 3,5-diiodo-<scp>L</scp>-tyrosine by compound II

Ralston, Isobel M.; Dunford, H. Brian

doi:10.1139/o80-170

Cited by 21 publications

(16 citation statements)

References 12 publications

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“…5 (28,29). CpdI can promote the formation of two tyrosyl radicals, as demonstrated with the horseradish peroxidase, another hemecontaining protein forming CpdI as the reactive species (30,31). Moreover, one of the major reactions observed between two tyrosyl radicals is the formation of a tyrosyl cross link between the carbon atoms positioned ortho with respect to the hydroxyl (32).…”

Section: Discussionmentioning

confidence: 96%

Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis

Belin

Fielding

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

190

355

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The gene encoding the cytochrome P450 CYP121 is essential for Mycobacterium tuberculosis. However, the CYP121 catalytic activity remains unknown. Here, we show that the cyclodipeptide cyclo(l-Tyr-l-Tyr) (cYY) binds to CYP121, and is efficiently converted into a single major product in a CYP121 activity assay containing spinach ferredoxin and ferredoxin reductase. NMR spectroscopy analysis of the reaction product shows that CYP121 catalyzes the formation of an intramolecular C-C bond between 2 tyrosyl carbon atoms of cYY resulting in a novel chemical entity. The X-ray structure of cYY-bound CYP121, solved at high resolution (1.4 Å), reveals one cYY molecule with full occupancy in the large active site cavity. One cYY tyrosyl approaches the heme and establishes a specific H-bonding network with Ser-237, Gln-385, Arg-386, and 3 water molecules, including the sixth iron ligand. These observations are consistent with low temperature EPR spectra of cYYbound CYP121 showing a change in the heme environment with the persistence of the sixth heme iron ligand. As the carbon atoms involved in the final C-C coupling are located 5.4 Å apart according to the CYP121-cYY complex crystal structure, we propose that C-C coupling is concomitant with substrate tyrosyl movements. This study provides insight into the catalytic activity, mechanism, and biological function of CYP121. Also, it provides clues for rational design of putative CYP121 substrate-based antimycobacterial agents.C-C coupling ͉ cyclopeptide

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Section: Discussionmentioning

confidence: 96%

Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis

Belin

Fielding

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

190

355

View full text Add to dashboard Cite

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“…After a delay time of 2.5 s, the formed HRP-II was allowed to react with varying concentrations of tempol. The reaction course was monitored by the decay of HRP-II at 425 nm (44). In all cases, k obs values were determined by using the single curve-fit equation of the instrument software.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of myeloperoxidase-mediated protein nitration by tempol: Kinetics, mechanism, and implications

Vaz

Augusto

2008

Proc. Natl. Acad. Sci. U.S.A.

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Despite the therapeutic potential of tempol (4-hydroxy-2,2,6,6-tetra-methyl-1-piperidinyloxy) and related nitroxides as antioxidants, their effects on peroxidase-mediated protein tyrosine nitration remain unexplored. This posttranslational protein modification is a biomarker of nitric oxide-derived oxidants, and, relevantly, it parallels tissue injury in animal models of inflammation and is attenuated by tempol treatment. Here, we examine tempol effects on ribonuclease (RNase) nitration mediated by myeloperoxidase (MPO), a mammalian enzyme that plays a central role in various inflammatory processes. Some experiments were also performed with horseradish peroxidase (HRP). We show that tempol efficiently inhibits peroxidase-mediated RNase nitration. For instance, 10 M tempol was able to inhibit by 90% the yield of 290 M 3-nitrotyrosine produced from 370 M RNase. The effect of tempol was not completely catalytic because part of it was consumed by recombination with RNase-tyrosyl radicals. The second-order rate constant of the reaction of tempol with MPO compound I and II were determined by stopped-flow kinetics as 3.3 ؋ 10 6 and 2.6 ؋ 10 4 M ؊1 s ؊1 , respectively (pH 7.4, 25°C); the corresponding HRP constants were orders of magnitude smaller. Time-dependent hydrogen peroxide and nitrite consumption and oxygen production in the incubations were quantified experimentally and modeled by kinetic simulations. The results indicate that tempol inhibits peroxidase-mediated RNase nitration mainly because of its reaction with nitrogen dioxide to produce the oxammonium cation, which, in turn, recycles back to tempol by reacting with hydrogen peroxide and superoxide radical to produce oxygen and regenerate nitrite. The implications for nitroxide antioxidant mechanisms are discussed.antioxidant ͉ tyrosine ͉ tyrosine nitration ͉ nitroxides ͉ nitric oxide-derived oxidants

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“…4). Tyrosine is oxidized by horseradish peroxidase compound I at a rate of 5.0 ϫ 10 4 M Ϫ1 s Ϫ1 (19) and compound II at a rate of 1.1 ϫ 10 3 M Ϫ1 s Ϫ1 (20). The observed tyrosyl radical ESR spectrum (Fig.…”

Section: Figmentioning

confidence: 96%

The Fate of the Oxidizing Tyrosyl Radical in the Presence of Glutathione and Ascorbate

Sturgeon

Sipe

Barr

et al. 1998

Journal of Biological Chemistry

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Cellular systems contain as much as millimolar concentrations of both ascorbate and GSH, although the GSH concentration is often 10-fold that of ascorbate. It has been proposed that GSH and superoxide dismutase (SOD) act in a concerted effort to eliminate biologically generated radicals. The tyrosyl radical (Tyr ⅐ ) generated by horseradish peroxidase in the presence of hydrogen peroxide can react with GSH to form the glutathione thiyl radical (GS ⅐ ). GS ⅐ can react with the glutathione anion (GS ؊ ) to form the disulfide radical anion (GSSG . ). This highly reactive disulfide radical anion will reduce molecular oxygen, forming superoxide and glutathione disulfide (GSSG). In a concerted effort, SOD will catalyze the dismutation of superoxide, resulting in the elimination of the radical. The physiological relevance of this GSH/SOD concerted effort is questionable. In a tyrosyl radical-generating system containing ascorbate (100 M) and GSH (8 mM), the ascorbate nearly eliminated oxygen consumption and diminished GS ⅐ formation. In the presence of ascorbate, the tyrosyl radical will oxidize ascorbate to form the ascorbate radical. When measuring the ascorbate radical directly using fast-flow electron spin resonance, only minor changes in the ascorbate radical electron spin resonance signal intensity occurred in the presence of GSH. These results indicate that in the presence of physiological concentrations of ascorbate and GSH, GSH is not involved in the detoxification pathway of oxidizing free radicals formed by peroxidases.

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Horseradish peroxidase. XLII. Oxidations of L-tyrosine and 3,5-diiodo-L-tyrosine by compound II

Cited by 21 publications

References 12 publications

Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis

Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis

Inhibition of myeloperoxidase-mediated protein nitration by tempol: Kinetics, mechanism, and implications

The Fate of the Oxidizing Tyrosyl Radical in the Presence of Glutathione and Ascorbate

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