9DK2

Lexapeptide dehydratase complex LxmKY, ATP bound

9DK2 の概要

• エントリーDOI: 10.2210/pdb9dk2/pdb
• 関連するPDBエントリー: 9DK1
• 分子名称: Kinase, Lyase, ADENOSINE-5'-TRIPHOSPHATE, ... (8 entities in total)
• 機能のキーワード: kinase, lyase, lanthipeptide dehydratase, complex, biosynthetic protein
• 由来する生物種: Streptomyces rochei; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83362.40

構造登録者

Randall, G.T.,Bashiri, G. (登録日: 2024-09-07, 公開日: 2024-12-04, 最終更新日: 2025-01-01)

主引用文献

Randall, G.T.,Grant-Mackie, E.S.,Chunkath, S.,Williams, E.T.,Middleditch, M.J.,Tao, M.,Harris, P.W.R.,Brimble, M.A.,Bashiri, G.
A Stable Dehydratase Complex Catalyzes the Formation of Dehydrated Amino Acids in a Class V Lanthipeptide.
Acs Chem.Biol., 19:2548-2556, 2024

PubMed Abstract: Lanthipeptides are ribosomally synthesized and post-translationally modified peptides that bear the characteristic lanthionine (Lan) or methyllanthionine (MeLan) thioether linkages. (Me)Lan moieties bestow lanthipeptides with robust stability and diverse antimicrobial, anticancer, and antiallodynic activities. Installation of (Me)Lan requires dehydration of serine and threonine residues to 2,3-dehydroalanine (Dha) and ()-2,3-dehydrobutyrine (Dhb), respectively. LxmK and LxmY enzymes comprise the biosynthetic machinery of a newly discovered class V lanthipeptide, lexapeptide, and are proposed to catalyze the dehydration of serine and threonine residues in the precursor peptide. We demonstrate that LxmK and LxmY form a stable dehydratase complex to dehydrate precursor peptides. In addition, we present crystal structures of the LxmKY heterodimer, revealing structural and mechanistic features that enable iterative phosphorylation and elimination by the LxmKY complex. These findings provide molecular insights into class V lanthionine synthetases and lay the foundation for their applications as enzymatic tools in the biosynthesis of exquisitely modified peptides.

PubMed: 39586055
DOI: 10.1021/acschembio.4c00637

実験手法

X-RAY DIFFRACTION (2.5 Å)