7KQ4

Structure of isethionate sulfite-lyase from Bilophila wadsworthia with glycerol bound

7KQ4 の概要

• エントリーDOI: 10.2210/pdb7kq4/pdb
• 分子名称: Isethionate sulfite-lyase, GLYCEROL (3 entities in total)
• 機能のキーワード: glycyl radical enzyme, isethionate-sulfite lyase, carbon-sulfur bond cleavage, microbiome, lyase
• 由来する生物種: Bilophila wadsworthia (strain 3_1_6)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 188347.58

構造登録者

Dawson, C.D.,Backman, L.R.F.,Drennan, C.L. (登録日: 2020-11-13, 公開日: 2021-04-07, 最終更新日: 2023-10-18)

主引用文献

Dawson, C.D.,Irwin, S.M.,Backman, L.R.F.,Le, C.,Wang, J.X.,Vennelakanti, V.,Yang, Z.,Kulik, H.J.,Drennan, C.L.,Balskus, E.P.
Molecular basis of C-S bond cleavage in the glycyl radical enzyme isethionate sulfite-lyase.
Cell Chem Biol, 28:1333-, 2021

PubMed Abstract: Desulfonation of isethionate by the bacterial glycyl radical enzyme (GRE) isethionate sulfite-lyase (IslA) generates sulfite, a substrate for respiration that in turn produces the disease-associated metabolite hydrogen sulfide. Here, we present a 2.7 Å resolution X-ray structure of wild-type IslA from Bilophila wadsworthia with isethionate bound. In comparison with other GREs, alternate positioning of the active site β strands allows for distinct residue positions to contribute to substrate binding. These structural differences, combined with sequence variations, create a highly tailored active site for the binding of the negatively charged isethionate substrate. Through the kinetic analysis of 14 IslA variants and computational analyses, we probe the mechanism by which radical chemistry is used for C-S bond cleavage. This work further elucidates the structural basis of chemistry within the GRE superfamily and will inform structure-based inhibitor design of IsIA and thus of microbial hydrogen sulfide production.

PubMed: 33773110
DOI: 10.1016/j.chembiol.2021.03.001

実験手法

X-RAY DIFFRACTION (2.261 Å)