7KQ3
Structure of isethionate sulfite-lyase from Bilophila wadsworthia with substrate isethionate bound
Summary for 7KQ3
| Entry DOI | 10.2210/pdb7kq3/pdb |
| Descriptor | Isethionate sulfite-lyase, 2-hydroxyethylsulfonic acid (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 | 4 |
| Total formula weight | 376831.31 |
| 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 Cited by 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: 33773110DOI: 10.1016/j.chembiol.2021.03.001 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.688 Å) |
Structure validation
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