9JML

NADP-dependent oxidoreductase complexed with NADP and substrate 1

これはPDB形式変換不可エントリーです。

9JML の概要

• エントリーDOI: 10.2210/pdb9jml/pdb
• 分子名称: NADP-dependent oxidoreductase, (1Z,3Z,5Z,7S,8R,9S,10S,11R,13R,15R,16Z,18Z,24S)-11-ethyl-2,7-dihydroxy-10-methyl-21,25-diazatetracyclo[22.2.1.08,15.09,13]heptacosa-1,3,5,16,18-pentaene-20,26,27-trione, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: alcohol dehydrogenase, complex, biosynthetic protein
• 由来する生物種: Lysobacter enzymogenes
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80362.72

構造登録者

Li, Y.,Zhu, D.,Xie, X.,Li, F.,Lu, M. (登録日: 2024-09-20, 公開日: 2025-06-18)

主引用文献

Xie, X.,Li, F.,Mu, Y.,Lu, M.,Luo, J.,Wang, H.,Shen, Y.,Du, L.,Zhu, D.,Li, Y.
Structural Basis for Medium-Chain Dehydrogenase/Reductase-Catalyzed Reductive Cyclization in Polycyclic Tetramate Macrolactam Biosynthesis.
J.Am.Chem.Soc., 147:19253-19261, 2025

PubMed Abstract: Few enzymes are known to catalyze reductive cyclizations via nucleophile-mediated C-C bond formation. Medium-chain dehydrogenases/reductases (MDRs) typically function as dehydrogenases or reductases. However, a distinct subclass of MDRs involved in polycyclic tetramate macrolactam (PoTeM) biosynthesis catalyzes reductive cyclizations via hydride-mediated C-C bond formation. Here, we present the apo and substrate-bound structures of OX4 and CftD, two enzymes responsible for the third ring formation in PoTeMs biosynthesis. Structural and mutational analysis reveal a catalytic mechanism wherein OX4 initiates a NADPH-dependent 1,6-reduction, followed by cyclization to form the C11-C22 bond, water-mediated protonation of the C7-carbonyl oxygen, and a final tautomerization to produce the cyclized product. Precise substrate positioning and stabilization of the enolate intermediate by the conserved residue W260 are critical for catalysis. These findings represent the first structural and mechanistic understanding of this newly identified cyclase subgroup and offer promising new avenues for enzyme engineering and natural product biosynthesis.

PubMed: 40406958
DOI: 10.1021/jacs.5c04971

実験手法

X-RAY DIFFRACTION (2.02 Å)