Evidence for heme oxygenase activity in a heme peroxidase.
The heme peroxidase and heme oxygenase enzymes share a common heme prosthetic group but catalyze fundamentally different reactions, the first being H(2)O(2)-dependent oxidation of substrate using an oxidized Compound I intermediate, and the second O(2)-dependent degradation of heme. It has been prop...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1826289880699764736 |
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| author | Badyal, S Eaton, G Mistry, S Pipirou, Z Basran, J Metcalfe, C Gumiero, A Handa, S Moody, P Raven, E |
| author_facet | Badyal, S Eaton, G Mistry, S Pipirou, Z Basran, J Metcalfe, C Gumiero, A Handa, S Moody, P Raven, E |
| author_sort | Badyal, S |
| collection | OXFORD |
| description | The heme peroxidase and heme oxygenase enzymes share a common heme prosthetic group but catalyze fundamentally different reactions, the first being H(2)O(2)-dependent oxidation of substrate using an oxidized Compound I intermediate, and the second O(2)-dependent degradation of heme. It has been proposed that these enzymes utilize a common reaction intermediate, a ferric hydroperoxide species, that sits at a crossroads in the mechanism and beyond which there are two mutually exclusive mechanistic pathways. Here, we present evidence to support this proposal in a heme peroxidase. Hence, we describe kinetic data for a variant of ascorbate peroxidase (W41A) which reacts slowly with tert-butyl hydroperoxide and does not form the usual peroxidase Compound I intermediate; instead, structural data show that a product is formed in which the heme has been cleaved at the alpha-meso position, analogous to the heme oxygenase mechanism. We interpret this to mean that the Compound I (peroxidase) pathway is shut down, so that instead the reaction intermediate diverts through the alternative (heme oxygenase) route. A mechanism for formation of the product is proposed and discussed in the light of what is known about the heme oxygenase reaction mechanism. |
| first_indexed | 2024-03-07T02:35:39Z |
| format | Journal article |
| id | oxford-uuid:a8b0967f-29e6-445f-a7ef-816e0160f4d2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:35:39Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:a8b0967f-29e6-445f-a7ef-816e0160f4d22022-03-27T03:03:22ZEvidence for heme oxygenase activity in a heme peroxidase.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a8b0967f-29e6-445f-a7ef-816e0160f4d2EnglishSymplectic Elements at Oxford2009Badyal, SEaton, GMistry, SPipirou, ZBasran, JMetcalfe, CGumiero, AHanda, SMoody, PRaven, EThe heme peroxidase and heme oxygenase enzymes share a common heme prosthetic group but catalyze fundamentally different reactions, the first being H(2)O(2)-dependent oxidation of substrate using an oxidized Compound I intermediate, and the second O(2)-dependent degradation of heme. It has been proposed that these enzymes utilize a common reaction intermediate, a ferric hydroperoxide species, that sits at a crossroads in the mechanism and beyond which there are two mutually exclusive mechanistic pathways. Here, we present evidence to support this proposal in a heme peroxidase. Hence, we describe kinetic data for a variant of ascorbate peroxidase (W41A) which reacts slowly with tert-butyl hydroperoxide and does not form the usual peroxidase Compound I intermediate; instead, structural data show that a product is formed in which the heme has been cleaved at the alpha-meso position, analogous to the heme oxygenase mechanism. We interpret this to mean that the Compound I (peroxidase) pathway is shut down, so that instead the reaction intermediate diverts through the alternative (heme oxygenase) route. A mechanism for formation of the product is proposed and discussed in the light of what is known about the heme oxygenase reaction mechanism. |
| spellingShingle | Badyal, S Eaton, G Mistry, S Pipirou, Z Basran, J Metcalfe, C Gumiero, A Handa, S Moody, P Raven, E Evidence for heme oxygenase activity in a heme peroxidase. |
| title | Evidence for heme oxygenase activity in a heme peroxidase. |
| title_full | Evidence for heme oxygenase activity in a heme peroxidase. |
| title_fullStr | Evidence for heme oxygenase activity in a heme peroxidase. |
| title_full_unstemmed | Evidence for heme oxygenase activity in a heme peroxidase. |
| title_short | Evidence for heme oxygenase activity in a heme peroxidase. |
| title_sort | evidence for heme oxygenase activity in a heme peroxidase |
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