9FCU

CysG(N-16)-H121A mutant in complex with SAH from Kitasatospora cystarginea

9FCU の概要

• エントリーDOI: 10.2210/pdb9fcu/pdb
• 関連するPDBエントリー: 9FCD
• 分子名称: SAM-dependent methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• 機能のキーワード: natural product biosynthesis, enzyme mechanism, metal ion interaction, molecular docking, structure function relationships, transferase
• 由来する生物種: Kitasatospora cystarginea
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 97397.62

構造登録者

Kuttenlochner, W.,Beller, P.,Kaysser, L.,Groll, M. (登録日: 2024-05-15, 公開日: 2024-08-21, 最終更新日: 2024-09-18)

主引用文献

Kuttenlochner, W.,Beller, P.,Kaysser, L.,Groll, M.
Deciphering the SAM- and metal-dependent mechanism of O-methyltransferases in cystargolide and belactosin biosynthesis: A structure-activity relationship study.
J.Biol.Chem., 300:107646-107646, 2024

PubMed Abstract: Cystargolides and belactosins are natural products with a distinct dipeptide structure and an electrophilic β-lactone warhead. They are known to inhibit proteases such as the proteasome or caseinolytic protease P, highlighting their potential in treating cancers and neurodegenerative diseases. Recent genetic analyses have shown homology between the biosynthetic pathways of the two inhibitors. Here, we characterize the O-methyltransferases BelI and CysG, which catalyze the initial step of β-lactone formation. Employing techniques such as crystallography, computational analysis, mutagenesis, and activity assays, we identified a His-His-Asp (HHD) motif in the active sites of the two enzymes, which is crucial for binding a catalytically active calcium ion. Our findings thus elucidate a conserved divalent metal-dependent mechanism in both biosynthetic pathways that distinguish BelI and CysG from previously characterized O-methyltransferases.

PubMed: 39121999
DOI: 10.1016/j.jbc.2024.107646

実験手法

X-RAY DIFFRACTION (1.85 Å)