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...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | JOUR |
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00278424_v106_n41_p17371_LewisBallester |
| Aporte de: |
| id |
todo:paper_00278424_v106_n41_p17371_LewisBallester |
|---|---|
| record_format |
dspace |
| spelling |
todo:paper_00278424_v106_n41_p17371_LewisBallester2023-10-03T14:38:01Z Evidence for a ferryl intermediate in a heme-based dioxygenase Lewis-Ballester, A. Batabyal, D. Egawa, T. Lu, C. Lin, Y. Marti, M.A. Capece, L. Estrin, D.A. Yeh, S.-R. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00278424_v106_n41_p17371_LewisBallester |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (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 |
JOUR |
| 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 |
| url |
http://hdl.handle.net/20.500.12110/paper_00278424_v106_n41_p17371_LewisBallester |
| work_keys_str_mv |
AT lewisballestera evidenceforaferrylintermediateinahemebaseddioxygenase AT batabyald evidenceforaferrylintermediateinahemebaseddioxygenase AT egawat evidenceforaferrylintermediateinahemebaseddioxygenase AT luc evidenceforaferrylintermediateinahemebaseddioxygenase AT liny evidenceforaferrylintermediateinahemebaseddioxygenase AT martima evidenceforaferrylintermediateinahemebaseddioxygenase AT capecel evidenceforaferrylintermediateinahemebaseddioxygenase AT estrinda evidenceforaferrylintermediateinahemebaseddioxygenase AT yehsr evidenceforaferrylintermediateinahemebaseddioxygenase |
| _version_ |
1782024747079434240 |