6NDX

Lysinoalanine cross-linked FlgE dimer from Treponema denticola

6NDX の概要

• エントリーDOI: 10.2210/pdb6ndx/pdb
• 関連するPDBエントリー: 6NDT 6NDV 6NDW
• 分子名称: Flagellar hook protein FlgE (3 entities in total)
• 機能のキーワード: hook, lysinoalanine, crosslinking, spirochetes, periodontal disease, flge, dehydroalanine, motor protein
• 由来する生物種: Treponema denticola; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 108982.71

構造登録者

Lynch, M.J.,Crane, B.R. (登録日: 2018-12-14, 公開日: 2019-08-14, 最終更新日: 2024-10-16)

主引用文献

Lynch, M.J.,Miller, M.,James, M.,Zhang, S.,Zhang, K.,Li, C.,Charon, N.W.,Crane, B.R.
Structure and chemistry of lysinoalanine crosslinking in the spirochaete flagella hook.
Nat.Chem.Biol., 15:959-965, 2019

PubMed Abstract: The flagellar hook protein FlgE from spirochaete bacteria self-catalyzes the formation of an unusual inter-subunit lysinoalanine (Lal) crosslink that is critical for cell motility. Unlike other known examples of Lal biosynthesis, conserved cysteine and lysine residues in FlgE spontaneously react to form Lal without the involvement of additional enzymes. Oligomerization of FlgE via its D0 and Dc domains drives assembly of the crosslinking site at the D1-D2 domain interface. Structures of the FlgE domain, dehydroalanine (DHA) intermediate and Lal crosslinked FlgE subunits reveal successive snapshots of the reaction. Cys178 flips from a buried configuration to release hydrogen sulfide (HS/HS) and produce DHA. Interface residues provide hydrogen bonds to anchor the active site, facilitate β-elimination of Cys178 and polarize the peptide backbone to activate DHA for reaction with Lys165. Cysteine-reactive molecules accelerate DHA formation, whereas nucleophiles can intercept the DHA intermediate, thereby indicating a potential for Lal crosslink inhibitors to combat spirochaetal diseases.

PubMed: 31406373
DOI: 10.1038/s41589-019-0341-3

実験手法

X-RAY DIFFRACTION (3.04 Å)