Iron oxidation state modulates active site structure in a heme peroxidase.
We have previously shown [Badyal, S. K., et al. (2006) J. Biol. Chem. 281, 24512-24520] that the distal histidine (His42) in the W41A variant of ascorbate peroxidase binds to the heme iron in the ferric form of the protein but that binding of the substrate triggers a conformational change in which H...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2008
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| _version_ | 1826280460621185024 |
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| author | Badyal, S Metcalfe, C Basran, J Efimov, I Moody, P Raven, E |
| author_facet | Badyal, S Metcalfe, C Basran, J Efimov, I Moody, P Raven, E |
| author_sort | Badyal, S |
| collection | OXFORD |
| description | We have previously shown [Badyal, S. K., et al. (2006) J. Biol. Chem. 281, 24512-24520] that the distal histidine (His42) in the W41A variant of ascorbate peroxidase binds to the heme iron in the ferric form of the protein but that binding of the substrate triggers a conformational change in which His42 dissociates from the heme. In this work, we show that this conformational rearrangement also occurs upon reduction of the heme iron. Thus, we present X-ray crystallographic data to show that reduction of the heme leads to dissociation of His42 from the iron in the ferrous form of W41A; spectroscopic and ligand binding data support this observation. Structural evidence indicates that heme reduction occurs through formation of a reduced, bis-histidine-ligated species that subsequently decays by dissociation of His42 from the heme. Collectively, the data provide clear evidence that conformational movement within the same heme active site can be controlled by both ligand binding and metal oxidation state. These observations are consistent with emerging data on other, more complex regulatory and sensing heme proteins, and the data are discussed in the context of our developing views in this area. |
| first_indexed | 2024-03-07T00:14:03Z |
| format | Journal article |
| id | oxford-uuid:7a381d16-e640-4d58-a88e-0e07ff8d53c3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:14:03Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:7a381d16-e640-4d58-a88e-0e07ff8d53c32022-03-26T20:42:32ZIron oxidation state modulates active site structure in a heme peroxidase.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7a381d16-e640-4d58-a88e-0e07ff8d53c3EnglishSymplectic Elements at Oxford2008Badyal, SMetcalfe, CBasran, JEfimov, IMoody, PRaven, EWe have previously shown [Badyal, S. K., et al. (2006) J. Biol. Chem. 281, 24512-24520] that the distal histidine (His42) in the W41A variant of ascorbate peroxidase binds to the heme iron in the ferric form of the protein but that binding of the substrate triggers a conformational change in which His42 dissociates from the heme. In this work, we show that this conformational rearrangement also occurs upon reduction of the heme iron. Thus, we present X-ray crystallographic data to show that reduction of the heme leads to dissociation of His42 from the iron in the ferrous form of W41A; spectroscopic and ligand binding data support this observation. Structural evidence indicates that heme reduction occurs through formation of a reduced, bis-histidine-ligated species that subsequently decays by dissociation of His42 from the heme. Collectively, the data provide clear evidence that conformational movement within the same heme active site can be controlled by both ligand binding and metal oxidation state. These observations are consistent with emerging data on other, more complex regulatory and sensing heme proteins, and the data are discussed in the context of our developing views in this area. |
| spellingShingle | Badyal, S Metcalfe, C Basran, J Efimov, I Moody, P Raven, E Iron oxidation state modulates active site structure in a heme peroxidase. |
| title | Iron oxidation state modulates active site structure in a heme peroxidase. |
| title_full | Iron oxidation state modulates active site structure in a heme peroxidase. |
| title_fullStr | Iron oxidation state modulates active site structure in a heme peroxidase. |
| title_full_unstemmed | Iron oxidation state modulates active site structure in a heme peroxidase. |
| title_short | Iron oxidation state modulates active site structure in a heme peroxidase. |
| title_sort | iron oxidation state modulates active site structure in a heme peroxidase |
| work_keys_str_mv | AT badyals ironoxidationstatemodulatesactivesitestructureinahemeperoxidase AT metcalfec ironoxidationstatemodulatesactivesitestructureinahemeperoxidase AT basranj ironoxidationstatemodulatesactivesitestructureinahemeperoxidase AT efimovi ironoxidationstatemodulatesactivesitestructureinahemeperoxidase AT moodyp ironoxidationstatemodulatesactivesitestructureinahemeperoxidase AT ravene ironoxidationstatemodulatesactivesitestructureinahemeperoxidase |