6ZP8

Yeast 20S proteasome in complex with glidobactin-like natural product HB335

6ZP8 の概要

• エントリーDOI: 10.2210/pdb6zp8/pdb
• 関連するPDBエントリー: 5CZ4
• 関連するBIRD辞書のPRD_ID: PRD_002578
• 分子名称: Proteasome subunit alpha type-2, Proteasome subunit beta type-4, Proteasome subunit beta type-5, ... (18 entities in total)
• 機能のキーワード: hydrolase-hydrolase inhibitor complex, proteasome, inhibitor, binding analysis, hydrolase
• 由来する生物種: Saccharomyces cerevisiae S288C; 詳細
• タンパク質・核酸の鎖数: 28
• 化学式量合計: 733222.38

構造登録者

Zhao, L.,Le Chapelain, C.,Brachmann, A.O.,Kaiser, M.,Groll, M.,Bode, H.B. (登録日: 2020-07-08, 公開日: 2021-05-19, 最終更新日: 2024-10-16)

主引用文献

Zhao, L.,Le Chapelain, C.,Brachmann, A.O.,Kaiser, M.,Groll, M.,Bode, H.B.
Activation, Structure, Biosynthesis and Bioactivity of Glidobactin-like Proteasome Inhibitors from Photorhabdus laumondii.
Chembiochem, 22:1582-1588, 2021

PubMed Abstract: The glidobactin-like natural products (GLNPs) glidobactin A and cepafungin I have been reported to be potent proteasome inhibitors and are regarded as promising candidates for anticancer drug development. Their biosynthetic gene cluster (BGC) plu1881-1877 is present in entomopathogenic Photorhabdus laumondii but silent under standard laboratory conditions. Here we show the largest subset of GLNPs, which are produced and identified after activation of the silent BGC in the native host and following heterologous expression of the BGC in Escherichia coli. Their chemical diversity results from a relaxed substrate specificity and flexible product release in the assembly line of GLNPs. Crystal structure analysis of the yeast proteasome in complex with new GLNPs suggests that the degree of unsaturation and the length of the aliphatic tail are critical for their bioactivity. The results in this study provide the basis to engineer the BGC for the generation of new GLNPs and to optimize these natural products resulting in potential drugs for cancer therapy.

PubMed: 33452852
DOI: 10.1002/cbic.202100014

実験手法

X-RAY DIFFRACTION (3 Å)