4OSO

The crystal structure of landomycin C-6 ketoreductase LanV with bound NADP and rabelomycin

Summary for 4OSO

• Entry DOI: 10.2210/pdb4oso/pdb
• Related: 4KWH 4KWI 4OSP
• Descriptor: Reductase homolog, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, rabelomycin, ... (5 entities in total)
• Functional Keywords: rossmann fold, ketoreductase, nadph binding, oxidoreductase-antibiotic complex, oxidoreductase/antibiotic
• Biological source: Streptomyces cyanogenus
• Total number of polymer chains: 2
• Total formula weight: 57377.82

Authors

Paananen, P.,Niiranen, L.,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

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)