7X0B

The structure of a Twitch Radical SAM Dehydrogenase SpeY

7X0B の概要

• エントリーDOI: 10.2210/pdb7x0b/pdb
• 分子名称: 4Fe-4S cluster-binding domain-containing protein, IRON/SULFUR CLUSTER, S-ADENOSYLMETHIONINE, ... (8 entities in total)
• 機能のキーワード: spectinomycin, twitch radical sam dehydrogenase, epimerase, biosynthetic protein
• 由来する生物種: Streptomyces spectabilis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75397.29

構造登録者

Hou, X.L.,Zhou, J.H. (登録日: 2022-02-21, 公開日: 2022-12-28, 最終更新日: 2023-11-29)

主引用文献

Zhang, J.,Hou, X.,Chen, Z.,Ko, Y.,Ruszczycky, M.W.,Chen, Y.,Zhou, J.,Liu, H.W.
Dioxane Bridge Formation during the Biosynthesis of Spectinomycin Involves a Twitch Radical S -Adenosyl Methionine Dehydrogenase That May Have Evolved from an Epimerase.
J.Am.Chem.Soc., 144:9910-9919, 2022

PubMed Abstract: Spectinomycin is a dioxane-bridged, tricyclic aminoglycoside produced by ATCC 27741. While the biosynthetic gene cluster for spectinomycin has been reported, the chemistry underlying construction of the dioxane ring is unknown. The twitch radical SAM enzyme SpeY from the cluster is shown here to catalyze dehydrogenation of the C2' alcohol of (2',3')-tetrahydrospectinomycin to yield (3')-dihydrospectinomycin as a likely biosynthetic intermediate. This reaction is radical-mediated and initiated via H atom abstraction from C2' of the substrate by the 5'-deoxyadenosyl radical equivalent generated upon reductive cleavage of SAM. Crystallographic analysis of the ternary Michaelis complex places serine-183 adjacent to C2' of the bound substrate opposite C5' of SAM. Mutation of this residue to cysteine converts SpeY to the corresponding C2' epimerase mirroring the opposite phenomenon observed in the homologous twitch radical SAM epimerase HygY from the hygromycin B biosynthetic pathway. Phylogenetic analysis suggests a relatively recent evolutionary branching of putative twitch radical SAM epimerases bearing homologous cysteine residues to generate the SpeY clade of enzymes.

PubMed: 35622017
DOI: 10.1021/jacs.2c02676

実験手法

X-RAY DIFFRACTION (2.02027524648 Å)