6YPZ

Promiscuous Reductase LugOII Catalyzes Keto-reduction at C1 during Lugdunomycin Biosynthesis

これはPDB形式変換不可エントリーです。

6YPZ の概要

• エントリーDOI: 10.2210/pdb6ypz/pdb
• 分子名称: Monooxygenase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: lugdunomycin, keto-reduction, short chain alcohol reductase, rossmann fold, antibiotic
• 由来する生物種: Streptomyces sp. QL37
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56042.39

構造登録者

Xiao, X.,Elsayed, S.S.,Wu, C.,van der Heul, H.,Prota, A.,Huang, J.,Guo, R.,Abrahams, J.P.,van Wezel, G.P. (登録日: 2020-04-16, 公開日: 2020-09-16, 最終更新日: 2024-01-24)

主引用文献

Xiao, X.,Elsayed, S.S.,Wu, C.,van der Heul, H.U.,Metsa-Ketela, M.,Du, C.,Prota, A.E.,Chen, C.C.,Liu, W.,Guo, R.T.,Abrahams, J.P.,van Wezel, G.P.
Functional and Structural Insights into a Novel Promiscuous Ketoreductase of the Lugdunomycin Biosynthetic Pathway.
Acs Chem.Biol., 15:2529-2538, 2020

PubMed Abstract: Angucyclines are a structurally diverse class of actinobacterial natural products defined by their varied polycyclic ring systems, which display a wide range of biological activities. We recently discovered lugdunomycin (), a highly rearranged polyketide antibiotic derived from the angucycline backbone that is synthesized via several yet unexplained enzymatic reactions. Here, we show via , , and structural analysis that the promiscuous reductase LugOII catalyzes both a C6 and an unprecedented C1 ketoreduction. This then sets the stage for the subsequent C-ring cleavage that is key to the rearranged scaffolds of . The 1.1 Å structures of LugOII in complex with either ligand 8--Methylrabelomycin () or 8--Methyltetrangomycin () and of apoenzyme were resolved, which revealed a canonical Rossman fold and a remarkable conformational change during substrate capture and release. Mutational analysis uncovered key residues for substrate access, position, and catalysis as well as specific determinants that control its dual functionality. The insights obtained in this work hold promise for the discovery and engineering of other promiscuous reductases that may be harnessed for the generation of novel biocatalysts for chemoenzymatic applications.

PubMed: 32840360
DOI: 10.1021/acschembio.0c00564

実験手法

X-RAY DIFFRACTION (1.08 Å)