7NM8

The crystal structure of the antimycin pathway standalone ketoreductase, AntM, in complex with NADPH

これはPDB形式変換不可エントリーです。

7NM8 の概要

• エントリーDOI: 10.2210/pdb7nm8/pdb
• 分子名称: Antimycin pathway standalone ketoreductase, AntM, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: ketoreductase, standalone, antimycin, nadph, oxidoreductase
• 由来する生物種: Streptomyces albus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30862.19

構造登録者

Fazal, A.,Hemsworth, G.R.,Webb, M.E.,Seipke, R.F. (登録日: 2021-02-23, 公開日: 2021-06-30, 最終更新日: 2024-01-31)

主引用文献

Fazal, A.,Hemsworth, G.R.,Webb, M.E.,Seipke, R.F.
A Standalone beta-Ketoreductase Acts Concomitantly with Biosynthesis of the Antimycin Scaffold.
Acs Chem.Biol., 16:1152-1158, 2021

PubMed Abstract: Antimycins are anticancer compounds produced by a hybrid nonribosomal peptide synthetase/polyketide synthase (NRPS/PKS) pathway. The biosynthesis of these compounds is well characterized, with the exception of the standalone β-ketoreductase enzyme AntM that is proposed to catalyze the reduction of the C8 carbonyl of the antimycin scaffold. Inactivation of and structural characterization suggested that rather than functioning as a post-PKS tailoring enzyme, AntM acts upon the terminal biosynthetic intermediate while it is tethered to the PKS acyl carrier protein. Mutational analysis identified two amino acid residues (Tyr185 and Phe223) that are proposed to serve as checkpoints controlling substrate access to the AntM active site. Aromatic checkpoint residues are conserved in uncharacterized standalone β-ketoreductases, indicating that they may also act concomitantly with synthesis of the scaffold. These data provide novel mechanistic insights into the functionality of standalone β-ketoreductases and will enable their reprogramming for combinatorial biosynthesis.

PubMed: 34151573
DOI: 10.1021/acschembio.1c00229

実験手法

X-RAY DIFFRACTION (1.7 Å)