4OSP

The crystal structure of urdamycin C-6 ketoreductase domain UrdMred with bound NADP and rabelomycin

4OSP の概要

• エントリーDOI: 10.2210/pdb4osp/pdb
• 関連するPDBエントリー: 4OSO
• 分子名称: Oxygenase-reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, rabelomycin, ... (4 entities in total)
• 機能のキーワード: rossmann fold, ketoreductase, nadph binding, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase-antibiotic complex, oxidoreductase/antibiotic
• 由来する生物種: Streptomyces fradiae
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 112395.62

構造登録者

Niiranen, L.,Paananen, P.,Patrikainen, P.,Metsa-Ketela, M. (登録日: 2014-02-13, 公開日: 2014-10-01, 最終更新日: 2023-09-20)

主引用文献

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

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: 25200607
DOI: 10.1016/j.chembiol.2014.07.017

実験手法

X-RAY DIFFRACTION (2.25 Å)