Modeling Type-1 Iodothyronine Deiodinase with Peptide-Based Aliphatic Diselenides: Potential Role of Highly Conserved His and Cys Residues as a General Acid Catalyst.

Autor: Arai K; Department of Chemistry, School of Science, Tokai University Kitakaname, Hiratsuka-shi, Kanagawa, 259-1292, Japan.; Institute of Advanced Biosciences, Tokai University Kitakaname, Hiratsuka-shi, Kanagawa, 259-1292, Japan., Toba H; Department of Chemistry, School of Science, Tokai University Kitakaname, Hiratsuka-shi, Kanagawa, 259-1292, Japan., Yamamoto N; Department of Chemistry, School of Science, Tokai University Kitakaname, Hiratsuka-shi, Kanagawa, 259-1292, Japan., Ito M; Department of Chemistry, School of Science, Tokai University Kitakaname, Hiratsuka-shi, Kanagawa, 259-1292, Japan., Mikami R; Department of Chemistry, School of Science, Tokai University Kitakaname, Hiratsuka-shi, Kanagawa, 259-1292, Japan.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2023 Jan 12; Vol. 29 (3), pp. e202202387. Date of Electronic Publication: 2022 Nov 21.
DOI: 10.1002/chem.202202387
Abstrakt: Type-1 iodothyronine deiodinase (ID-1) catalyzes the reductive elimination of 5'-I and 5-I on the phenolic and tyrosyl rings of thyroxine (T4), respectively. Chemically verifying whether I atoms with different chemical properties undergo deiodination through a common mechanism is challenging. Herein, we report the modeling of ID-1 using aliphatic diselenide (Se-Se) and selenenylsulfide (Se-S) compounds. Mechanistic investigations of deiodination using the ID-1-like reagents suggested that the 5'-I and 5-I deiodinations proceed via the same mechanism through an unstable intermediate containing a Se⋅⋅⋅I halogen bond between a selenolate anion, reductively produced from Se-Se (or Se-S) in the compound, and an I atom in T4. Moreover, imidazolium and thiol groups, which may act as general acid catalysts, promoted the heterolytic cleavage of the C-I bond in the Se⋅⋅⋅I intermediate, which is the rate-determining step, by donating a proton to the C atom.
(© 2022 Wiley-VCH GmbH.)
Databáze: MEDLINE
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