Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases.
Iron (II)/2-oxoglutarate (2-OG)-dependent oxygenases catalyse oxidative reactions in a range of metabolic processes including the hydroxylation of proline and lysine residues during the post-translational modification of collagen. 2-OG oxygenases commonly require ascorbate for full activity. In the...
| Hoofdauteurs: | , , , , |
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| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
2001
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| _version_ | 1826264658560942080 |
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| author | Clifton, I Hsueh, L Baldwin, J Harlos, K Schofield, C |
| author_facet | Clifton, I Hsueh, L Baldwin, J Harlos, K Schofield, C |
| author_sort | Clifton, I |
| collection | OXFORD |
| description | Iron (II)/2-oxoglutarate (2-OG)-dependent oxygenases catalyse oxidative reactions in a range of metabolic processes including the hydroxylation of proline and lysine residues during the post-translational modification of collagen. 2-OG oxygenases commonly require ascorbate for full activity. In the vitamin C deficient disease, scurvy, reduced activity of 2-OG oxygenases results in impaired formation of collagen. Here we report the crystal structure of bacterial proline 3-hydroxylase from Streptomyces sp., an enzyme which hydroxylates proline at position 3, the first of a 2-OG oxygenase catalysing oxidation of a free alpha-amino acid. Structures were obtained for the enzyme in the absence of iron (to 2.3A resolution, R=20.2%, Rfree=25.3%) and that complexed to iron (II) (to 2.4A resolution, R=19.8%, Rfree=22.6%). The structure contains conserved motifs present in other 2-OG oxygenases including a 'jelly roll' beta strand core and residues binding iron and 2-oxoglutarate, consistent with divergent evolution within the extended family. The structure differs significantly from many other 2-OG oxygenases in possessing a discrete C-terminal helical domain. Analysis of the structure suggests a model for proline binding and a mechanism for uncoupling of proline and 2-OG turnover. |
| first_indexed | 2024-03-06T20:11:23Z |
| format | Journal article |
| id | oxford-uuid:2aaa71f5-41f7-43dc-8aee-5ff7f86c60d8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:11:23Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:2aaa71f5-41f7-43dc-8aee-5ff7f86c60d82022-03-26T12:26:28ZStructure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2aaa71f5-41f7-43dc-8aee-5ff7f86c60d8EnglishSymplectic Elements at Oxford2001Clifton, IHsueh, LBaldwin, JHarlos, KSchofield, CIron (II)/2-oxoglutarate (2-OG)-dependent oxygenases catalyse oxidative reactions in a range of metabolic processes including the hydroxylation of proline and lysine residues during the post-translational modification of collagen. 2-OG oxygenases commonly require ascorbate for full activity. In the vitamin C deficient disease, scurvy, reduced activity of 2-OG oxygenases results in impaired formation of collagen. Here we report the crystal structure of bacterial proline 3-hydroxylase from Streptomyces sp., an enzyme which hydroxylates proline at position 3, the first of a 2-OG oxygenase catalysing oxidation of a free alpha-amino acid. Structures were obtained for the enzyme in the absence of iron (to 2.3A resolution, R=20.2%, Rfree=25.3%) and that complexed to iron (II) (to 2.4A resolution, R=19.8%, Rfree=22.6%). The structure contains conserved motifs present in other 2-OG oxygenases including a 'jelly roll' beta strand core and residues binding iron and 2-oxoglutarate, consistent with divergent evolution within the extended family. The structure differs significantly from many other 2-OG oxygenases in possessing a discrete C-terminal helical domain. Analysis of the structure suggests a model for proline binding and a mechanism for uncoupling of proline and 2-OG turnover. |
| spellingShingle | Clifton, I Hsueh, L Baldwin, J Harlos, K Schofield, C Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases. |
| title | Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases. |
| title_full | Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases. |
| title_fullStr | Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases. |
| title_full_unstemmed | Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases. |
| title_short | Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases. |
| title_sort | structure of proline 3 hydroxylase evolution of the family of 2 oxoglutarate dependent oxygenases |
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