6E6T

Dieckmann cyclase, NcmC, bound to cerulenin

6E6T の概要

• エントリーDOI: 10.2210/pdb6e6t/pdb
• 分子名称: NcmC, SULFATE ION, (4S,5R)-4,5-dihydroxy-5-[(3E,6E)-octa-3,6-dien-1-yl]pyrrolidin-2-one, ... (4 entities in total)
• 機能のキーワード: dieckmann cyclase, off-loading, dieckmann condensation, lyase-antibiotic complex, lyase/antibiotic
• 由来する生物種: Saccharothrix syringae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58271.46

構造登録者

Cogan, D.P.,Nair, S.K. (登録日: 2018-07-25, 公開日: 2019-07-31, 最終更新日: 2024-10-23)

主引用文献

Cogan, D.P.,Ly, J.,Nair, S.K.
Structural Basis for Enzymatic Off-Loading of Hybrid Polyketides by Dieckmann Condensation.
Acs Chem.Biol., 2020

PubMed Abstract: While several bioactive natural products that contain tetramate or pyridone heterocycles have been described, information on the enzymology underpinning these functionalities has been limited. Here we biochemically characterize an off-loading Dieckmann cyclase, NcmC, that installs the tetramate headgroup in nocamycin, a hybrid polyketide/nonribosomal peptide natural product. Crystal structures of the enzyme (1.6 Å) and its covalent complex with the epoxide cerulenin (1.6 Å) guide additional structure-based mutagenesis and product-profile analyses. Our results offer mechanistic insights into how the conserved thioesterase-like scaffold has been adapted to perform a new chemical reaction, namely, heterocyclization. Additional bioinformatics combined with docking and modeling identifies likely candidates for heterocycle formation in underexplored gene clusters and uncovers a modular basis of substrate recognition by the two subdomains of these Dieckmann cyclases.

PubMed: 33017142
DOI: 10.1021/acschembio.0c00579

実験手法

X-RAY DIFFRACTION (1.6 Å)