7KQ4

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

Summary for 7KQ4

• Entry DOI: 10.2210/pdb7kq4/pdb
• Descriptor: Isethionate sulfite-lyase, GLYCEROL (3 entities in total)
• Functional Keywords: glycyl radical enzyme, isethionate-sulfite lyase, carbon-sulfur bond cleavage, microbiome, lyase
• Biological source: Bilophila wadsworthia (strain 3_1_6)
• Total number of polymer chains: 2
• Total formula weight: 188347.58

Authors

Dawson, C.D.,Backman, L.R.F.,Drennan, C.L. (deposition date: 2020-11-13, release date: 2021-04-07, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.261 Å)