Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase.
The X-ray crystal structure of Mycobacterium tuberculosis shikimate kinase (SK) with bound shikimate and adenosine diphosphate (ADP) has been determined to a resolution of 2.15 A. The binding of shikimate in a shikimate kinase crystal structure has not previously been reported. The substrate binds i...
| Váldodahkkit: | , , , , , , |
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| Materiálatiipa: | Journal article |
| Giella: | English |
| Almmustuhtton: |
2004
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| _version_ | 1826262994743459840 |
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| author | Dhaliwal, B Nichols, C Ren, J Lockyer, M Charles, I Hawkins, A Stammers, D |
| author_facet | Dhaliwal, B Nichols, C Ren, J Lockyer, M Charles, I Hawkins, A Stammers, D |
| author_sort | Dhaliwal, B |
| collection | OXFORD |
| description | The X-ray crystal structure of Mycobacterium tuberculosis shikimate kinase (SK) with bound shikimate and adenosine diphosphate (ADP) has been determined to a resolution of 2.15 A. The binding of shikimate in a shikimate kinase crystal structure has not previously been reported. The substrate binds in a pocket lined with hydrophobic residues and interacts with several highly conserved charged residues including Asp34, Arg58, Glu61 and Arg136 which project into the cavity. Comparisons of our ternary SK-ADP-shikimate complex with an earlier binary SK-ADP complex show that conformational changes occur on shikimate binding with the substrate-binding domain rotating by 10 degrees. Detailed knowledge of shikimate binding is an important step in the design of inhibitors of SK, which have potential as novel anti-tuberculosis agents. |
| first_indexed | 2024-03-06T19:44:38Z |
| format | Journal article |
| id | oxford-uuid:21da1fb7-b47d-4dc2-83a5-f4fd2f0463f4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:44:38Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:21da1fb7-b47d-4dc2-83a5-f4fd2f0463f42022-03-26T11:35:37ZCrystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:21da1fb7-b47d-4dc2-83a5-f4fd2f0463f4EnglishSymplectic Elements at Oxford2004Dhaliwal, BNichols, CRen, JLockyer, MCharles, IHawkins, AStammers, DThe X-ray crystal structure of Mycobacterium tuberculosis shikimate kinase (SK) with bound shikimate and adenosine diphosphate (ADP) has been determined to a resolution of 2.15 A. The binding of shikimate in a shikimate kinase crystal structure has not previously been reported. The substrate binds in a pocket lined with hydrophobic residues and interacts with several highly conserved charged residues including Asp34, Arg58, Glu61 and Arg136 which project into the cavity. Comparisons of our ternary SK-ADP-shikimate complex with an earlier binary SK-ADP complex show that conformational changes occur on shikimate binding with the substrate-binding domain rotating by 10 degrees. Detailed knowledge of shikimate binding is an important step in the design of inhibitors of SK, which have potential as novel anti-tuberculosis agents. |
| spellingShingle | Dhaliwal, B Nichols, C Ren, J Lockyer, M Charles, I Hawkins, A Stammers, D Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase. |
| title | Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase. |
| title_full | Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase. |
| title_fullStr | Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase. |
| title_full_unstemmed | Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase. |
| title_short | Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase. |
| title_sort | crystallographic studies of shikimate binding and induced conformational changes in mycobacterium tuberculosis shikimate kinase |
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