8WGO

Cryo-EM structure of ClassIII Lanthipeptide modification enzyme PneKC in the presence of PneA and GTPrS.

8WGO の概要

• エントリーDOI: 10.2210/pdb8wgo/pdb
• EMDBエントリー: 37514
• 分子名称: Protein kinase domain-containing protein, SapB/AmfS family lantipeptide, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: lanthibiotic, ripps, lankc, cryoem, antimicrobial peptides, antiviral peptides., antimicrobial protein
• 由来する生物種: Streptococcus pneumoniae; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 206796.29

構造登録者

Li, Y.,Luo, M.,Shao, K.,Li, J. (登録日: 2023-09-22, 公開日: 2024-08-28, 最終更新日: 2025-07-02)

主引用文献

Li, Y.,Shao, K.,Li, Z.,Zhu, K.,Gan, B.K.,Shi, J.,Xiao, Y.,Luo, M.
Mechanistic insights into lanthipeptide modification by a distinct subclass of LanKC enzyme that forms dimers.
Nat Commun, 15:7090-7090, 2024

PubMed Abstract: Naturally occurring lanthipeptides, peptides post-translationally modified by various enzymes, hold significant promise as antibiotics. Despite extensive biochemical and structural studies, the events preceding peptide modification remain poorly understood. Here, we identify a distinct subclass of lanthionine synthetase KC (LanKC) enzymes with distinct structural and functional characteristics. We show that PneKC, a member of this subclass, forms a dimer and possesses GTPase activity. Through three cryo-EM structures of PneKC, we illustrate different stages of peptide PneA binding, from initial recognition to full binding. Our structures show the kinase domain complexed with the PneA core peptide and GTPγS, a phosphate-bound lyase domain, and an unconventional cyclase domain. The leader peptide of PneA interact with a gate loop, transitioning from an extended to a helical conformation. We identify a dimerization hot spot and propose a "negative cooperativity" mechanism toggling the enzyme between tense and relaxed conformation. Additionally, we identify an important salt bridge in the cyclase domain, differing from those in in conventional cyclase domains. These residues are highly conserved in the LanKC subclass and are part of two signature motifs. These results unveil potential differences in lanthipeptide modification enzymes assembly and deepen our understanding of allostery in these multifunctional enzymes.

PubMed: 39154050
DOI: 10.1038/s41467-024-51600-6

実験手法

ELECTRON MICROSCOPY (3.7 Å)