The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold.
dUTPase is an essential enzyme involved with nucleotide metabolism and replication. We report here the X-ray structure of Trypanosoma cruzi dUTPase in its native conformation and as a complex with dUDP. These reveal a novel protein fold that displays no structural similarities to previously describe...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2004
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| _version_ | 1797076431155494912 |
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| author | Harkiolaki, M Dodson, E Bernier-Villamor, V Turkenburg, J González-Pacanowska, D Wilson, K |
| author_facet | Harkiolaki, M Dodson, E Bernier-Villamor, V Turkenburg, J González-Pacanowska, D Wilson, K |
| author_sort | Harkiolaki, M |
| collection | OXFORD |
| description | dUTPase is an essential enzyme involved with nucleotide metabolism and replication. We report here the X-ray structure of Trypanosoma cruzi dUTPase in its native conformation and as a complex with dUDP. These reveal a novel protein fold that displays no structural similarities to previously described dUTPases. The molecular unit is a dimer with two active sites. Nucleotide binding promotes extensive structural rearrangements, secondary structure remodeling, and rigid body displacements of 20 A or more, which effectively bury the substrate within the enzyme core for the purpose of hydrolysis. The molecular complex is a trapped enzyme-substrate arrangement which clearly demonstrates structure-induced specificity and catalytic potential. This enzyme is a novel dUTPase and therefore a potential drug target in the treatment of Chagas' disease. |
| first_indexed | 2024-03-07T00:03:40Z |
| format | Journal article |
| id | oxford-uuid:76d41482-ea58-43ff-8648-8c283e6ab5cf |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:03:40Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:76d41482-ea58-43ff-8648-8c283e6ab5cf2022-03-26T20:18:52ZThe crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:76d41482-ea58-43ff-8648-8c283e6ab5cfEnglishSymplectic Elements at Oxford2004Harkiolaki, MDodson, EBernier-Villamor, VTurkenburg, JGonzález-Pacanowska, DWilson, KdUTPase is an essential enzyme involved with nucleotide metabolism and replication. We report here the X-ray structure of Trypanosoma cruzi dUTPase in its native conformation and as a complex with dUDP. These reveal a novel protein fold that displays no structural similarities to previously described dUTPases. The molecular unit is a dimer with two active sites. Nucleotide binding promotes extensive structural rearrangements, secondary structure remodeling, and rigid body displacements of 20 A or more, which effectively bury the substrate within the enzyme core for the purpose of hydrolysis. The molecular complex is a trapped enzyme-substrate arrangement which clearly demonstrates structure-induced specificity and catalytic potential. This enzyme is a novel dUTPase and therefore a potential drug target in the treatment of Chagas' disease. |
| spellingShingle | Harkiolaki, M Dodson, E Bernier-Villamor, V Turkenburg, J González-Pacanowska, D Wilson, K The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold. |
| title | The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold. |
| title_full | The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold. |
| title_fullStr | The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold. |
| title_full_unstemmed | The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold. |
| title_short | The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold. |
| title_sort | crystal structure of trypanosoma cruzi dutpase reveals a novel dutp dudp binding fold |
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