4OSP
The crystal structure of urdamycin C-6 ketoreductase domain UrdMred with bound NADP and rabelomycin
Summary for 4OSP
| Entry DOI | 10.2210/pdb4osp/pdb |
| Related | 4OSO |
| Descriptor | Oxygenase-reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, rabelomycin, ... (4 entities in total) |
| Functional Keywords | rossmann fold, ketoreductase, nadph binding, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase-antibiotic complex, oxidoreductase/antibiotic |
| Biological source | Streptomyces fradiae |
| Total number of polymer chains | 4 |
| Total formula weight | 112395.62 |
| Authors | Niiranen, L.,Paananen, P.,Patrikainen, P.,Metsa-Ketela, M. (deposition date: 2014-02-13, release date: 2014-10-01, Last modification date: 2023-09-20) |
| Primary citation | Patrikainen, P.,Niiranen, L.,Thapa, K.,Paananen, P.,Tahtinen, P.,Mantsala, P.,Niemi, J.,Metsa-Ketela, M. Structure-based engineering of angucyclinone 6-ketoreductases. Chem.Biol., 21:1381-1391, 2014 Cited by PubMed Abstract: Angucyclines are tetracyclic polyketides produced by Streptomyces bacteria that exhibit notable biological activities. The great diversity of angucyclinones is generated in tailoring reactions, which modify the common benz[a]anthraquinone carbon skeleton. In particular, the opposite stereochemistry of landomycins and urdamycins/gaudimycins at C-6 is generated by the short-chain alcohol dehydrogenases/reductases LanV and UrdMred/CabV, respectively. Here we present crystal structures of LanV and UrdMred in complex with NADP(+) and the product analog rabelomycin, which enabled us to identify four regions associated with the functional differentiation. The structural analysis was confirmed in chimeragenesis experiments focusing on these regions adjacent to the active site cavity, which led to reversal of the activities of LanV and CabV. The results surprisingly indicated that the conformation of the substrate and the stereochemical outcome of 6-ketoreduction appear to be intimately linked. PubMed: 25200607DOI: 10.1016/j.chembiol.2014.07.017 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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