4LRE
Phosphopentomutase soaked with 2,3-dideoxyribose 5-phosphate
Summary for 4LRE
| Entry DOI | 10.2210/pdb4lre/pdb |
| Related | 3M8Z 3TWZ 3TX0 3UN3 4LR7 4LR8 4LR9 4LRA 4LRB 4LRC 4LRD 4LRF |
| Descriptor | Phosphopentomutase, MANGANESE (II) ION, 2,3-dideoxy-5-O-phosphono-alpha-D-ribofuranose, ... (4 entities in total) |
| Functional Keywords | alkaline phosphatase family, isomerase |
| Biological source | Bacillus cereus |
| Total number of polymer chains | 3 |
| Total formula weight | 140188.62 |
| Authors | Birmingham, W.A.,Starbird, C.A.,Panosian, T.D.,Nannemann, D.P.,Iverson, T.M.,Bachmann, B.O. (deposition date: 2013-07-19, release date: 2013-07-31, Last modification date: 2024-11-27) |
| Primary citation | Birmingham, W.R.,Starbird, C.A.,Panosian, T.D.,Nannemann, D.P.,Iverson, T.M.,Bachmann, B.O. Bioretrosynthetic construction of a didanosine biosynthetic pathway. Nat.Chem.Biol., 10:392-399, 2014 Cited by PubMed Abstract: Concatenation of engineered biocatalysts into multistep pathways markedly increases their utility, but the development of generalizable assembly methods remains a major challenge. Herein we evaluate 'bioretrosynthesis', which is an application of the retrograde evolution hypothesis, for biosynthetic pathway construction. To test bioretrosynthesis, we engineered a pathway for synthesis of the antiretroviral nucleoside analog didanosine (2',3'-dideoxyinosine). Applying both directed evolution- and structure-based approaches, we began pathway construction with a retro-extension from an engineered purine nucleoside phosphorylase and evolved 1,5-phosphopentomutase to accept the substrate 2,3-dideoxyribose 5-phosphate with a 700-fold change in substrate selectivity and threefold increased turnover in cell lysate. A subsequent retrograde pathway extension, via ribokinase engineering, resulted in a didanosine pathway with a 9,500-fold change in nucleoside production selectivity and 50-fold increase in didanosine production. Unexpectedly, the result of this bioretrosynthetic step was not a retro-extension from phosphopentomutase but rather the discovery of a fortuitous pathway-shortening bypass via the engineered ribokinase. PubMed: 24657930DOI: 10.1038/nchembio.1494 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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