3LZC

Crystal structure of Dph2 from Pyrococcus horikoshii

3LZC の概要

• エントリーDOI: 10.2210/pdb3lzc/pdb
• 関連するPDBエントリー: 3LZD
• 分子名称: Dph2 (2 entities in total)
• 機能のキーワード: diphthamide biosynthesis, radical sam enzyme, gene triplication, biosynthetic protein
• 由来する生物種: Pyrococcus horikoshii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 85076.58

構造登録者

Zhang, Y.,Zhu, X.,Torelli, A.T.,Lee, M.,Dzikovski, B.,Koralewski, R.M.,Wang, E.,Freed, J.,Krebs, C.,Lin, H.,Ealick, S.E. (登録日: 2010-03-01, 公開日: 2010-06-23, 最終更新日: 2024-02-21)

主引用文献

Zhang, Y.,Zhu, X.,Torelli, A.T.,Lee, M.,Dzikovski, B.,Koralewski, R.M.,Wang, E.,Freed, J.,Krebs, C.,Ealick, S.E.,Lin, H.
Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme.
Nature, 465:891-896, 2010

PubMed Abstract: Archaeal and eukaryotic translation elongation factor 2 contain a unique post-translationally modified histidine residue called diphthamide, which is the target of diphtheria toxin. The biosynthesis of diphthamide was proposed to involve three steps, with the first being the formation of a C-C bond between the histidine residue and the 3-amino-3-carboxypropyl group of S-adenosyl-l-methionine (SAM). However, further details of the biosynthesis remain unknown. Here we present structural and biochemical evidence showing that the first step of diphthamide biosynthesis in the archaeon Pyrococcus horikoshii uses a novel iron-sulphur-cluster enzyme, Dph2. Dph2 is a homodimer and each of its monomers can bind a [4Fe-4S] cluster. Biochemical data suggest that unlike the enzymes in the radical SAM superfamily, Dph2 does not form the canonical 5'-deoxyadenosyl radical. Instead, it breaks the C(gamma,Met)-S bond of SAM and generates a 3-amino-3-carboxypropyl radical. Our results suggest that P. horikoshii Dph2 represents a previously unknown, SAM-dependent, [4Fe-4S]-containing enzyme that catalyses unprecedented chemistry.

PubMed: 20559380
DOI: 10.1038/nature09138

実験手法

X-RAY DIFFRACTION (2.261 Å)