Artículo

Lewis-Ballester, A.; Batabyal, D.; Egawa, T.; Lu, C.; Lin, Y.; Marti, M.A.; Capece, L.; Estrin, D.A.; Yeh, S.-R. "Evidence for a ferryl intermediate in a heme-based dioxygenase" (2009) Proceedings of the National Academy of Sciences of the United States of America. 106(41):17371-17376
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Abstract:

In contrast to the wide spectrum of cytochrome P450 monooxygenases, there are only 2 heme-based dioxygenases in humans: tryptophan dioxygenase (hTDO) and indoleamine 2,3-dioxygenase (hIDO). hTDO and hIDO catalyze the same oxidative ring cleavage reaction of L-tryptophan to N-formyl kynurenine, the initial and rate-limiting step of the kynurenine pathway. Despite immense interest, the mechanism by which the 2 enzymes execute the dioxygenase reaction remains elusive. Here, we report experimental evidence for a key ferryl intermediate of hIDO that supports a mechanism in which the 2 atoms of dioxygen are inserted into the substrate via a consecutive 2-step reaction. This finding introduces a paradigm shift in our understanding of the heme-based dioxygenase chemistry, which was previously believed to proceed via simultaneous incorporation of both atoms of dioxygen into the substrate. The ferryl intermediate is not observable during the hTDO reaction, highlighting the structural differences between the 2 dioxygenases, as well as the importance of stereoelectronic factors in modulating the reactions.

Registro:

Documento: Artículo
Título:Evidence for a ferryl intermediate in a heme-based dioxygenase
Autor:Lewis-Ballester, A.; Batabyal, D.; Egawa, T.; Lu, C.; Lin, Y.; Marti, M.A.; Capece, L.; Estrin, D.A.; Yeh, S.-R.
Filiación:Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, United States
Departamento de Química Inorgánica, Analítica Y Química Física, Instituto de Química de Los Materiales, Medio Ambiente Y Energía, Universidad de Buenos Aires, Buenos Aires, C1428EHA, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EHA, Argentina
Palabras clave:Indoleamine 2,3-dioxygenase; Reasonance raman spectroscopy; Tryptophan dioxygenase; indoleamine 2,3 dioxygenase; oxygen; tryptophan 2,3 dioxygenase; article; atom; controlled study; enzyme chemistry; enzyme conformation; enzyme mechanism; enzyme regulation; enzyme structure; kinetics; priority journal; Raman spectrometry; Computer Simulation; Crystallography, X-Ray; Dioxygenases; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kinetics; Kynurenine; Spectrum Analysis, Raman; Tryptophan
Año:2009
Volumen:106
Número:41
Página de inicio:17371
Página de fin:17376
DOI: http://dx.doi.org/10.1073/pnas.0906655106
Título revista:Proceedings of the National Academy of Sciences of the United States of America
Título revista abreviado:Proc. Natl. Acad. Sci. U. S. A.
ISSN:00278424
CODEN:PNASA
CAS:oxygen, 7782-44-7; tryptophan 2,3 dioxygenase, 9014-51-1; Dioxygenases, 1.13.11.-; Indoleamine-Pyrrole 2,3,-Dioxygenase, 1.13.11.42; Kynurenine, 343-65-7; N'-formylkynurenine, 1022-31-7; Tryptophan, 73-22-3
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00278424_v106_n41_p17371_LewisBallester.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v106_n41_p17371_LewisBallester

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Citas:

---------- APA ----------
Lewis-Ballester, A., Batabyal, D., Egawa, T., Lu, C., Lin, Y., Marti, M.A., Capece, L.,..., Yeh, S.-R. (2009) . Evidence for a ferryl intermediate in a heme-based dioxygenase. Proceedings of the National Academy of Sciences of the United States of America, 106(41), 17371-17376.
http://dx.doi.org/10.1073/pnas.0906655106
---------- CHICAGO ----------
Lewis-Ballester, A., Batabyal, D., Egawa, T., Lu, C., Lin, Y., Marti, M.A., et al. "Evidence for a ferryl intermediate in a heme-based dioxygenase" . Proceedings of the National Academy of Sciences of the United States of America 106, no. 41 (2009) : 17371-17376.
http://dx.doi.org/10.1073/pnas.0906655106
---------- MLA ----------
Lewis-Ballester, A., Batabyal, D., Egawa, T., Lu, C., Lin, Y., Marti, M.A., et al. "Evidence for a ferryl intermediate in a heme-based dioxygenase" . Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 41, 2009, pp. 17371-17376.
http://dx.doi.org/10.1073/pnas.0906655106
---------- VANCOUVER ----------
Lewis-Ballester, A., Batabyal, D., Egawa, T., Lu, C., Lin, Y., Marti, M.A., et al. Evidence for a ferryl intermediate in a heme-based dioxygenase. Proc. Natl. Acad. Sci. U. S. A. 2009;106(41):17371-17376.
http://dx.doi.org/10.1073/pnas.0906655106