Evidence for a ferryl intermediate in a heme-based dioxygenase
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 i...
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2009
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00278424_v106_n41_p17371_LewisBallester http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00278424_v106_n41_p17371_LewisBallester_oai |
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I28-R145-paper_00278424_v106_n41_p17371_LewisBallester_oai2020-10-19 Lewis-Ballester, A. Batabyal, D. Egawa, T. Lu, C. Lin, Y. Marti, M.A. Capece, L. Estrin, D.A. Yeh, S.-R. 2009 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. Fil:Marti, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Capece, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. application/pdf http://hdl.handle.net/20.500.12110/paper_00278424_v106_n41_p17371_LewisBallester info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar Proc. Natl. Acad. Sci. U. S. A. 2009;106(41):17371-17376 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 Evidence for a ferryl intermediate in a heme-based dioxygenase info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00278424_v106_n41_p17371_LewisBallester_oai |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-145 |
| collection |
Repositorio Digital de la Universidad de Buenos Aires (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
Artículo Artículo publishedVersion |
| author |
Lewis-Ballester, A. Batabyal, D. Egawa, T. Lu, C. Lin, Y. Marti, M.A. Capece, L. Estrin, D.A. Yeh, S.-R. |
| author_facet |
Lewis-Ballester, A. Batabyal, D. Egawa, T. Lu, C. Lin, Y. Marti, M.A. Capece, L. Estrin, D.A. Yeh, S.-R. |
| author_sort |
Lewis-Ballester, A. |
| title |
Evidence for a ferryl intermediate in a heme-based dioxygenase |
| title_short |
Evidence for a ferryl intermediate in a heme-based dioxygenase |
| title_full |
Evidence for a ferryl intermediate in a heme-based dioxygenase |
| title_fullStr |
Evidence for a ferryl intermediate in a heme-based dioxygenase |
| title_full_unstemmed |
Evidence for a ferryl intermediate in a heme-based dioxygenase |
| title_sort |
evidence for a ferryl intermediate in a heme-based dioxygenase |
| publishDate |
2009 |
| url |
http://hdl.handle.net/20.500.12110/paper_00278424_v106_n41_p17371_LewisBallester http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00278424_v106_n41_p17371_LewisBallester_oai |
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| _version_ |
1766026619967766528 |