4ttc
From Proteopedia
Crystal structure of homo sapiens IODOTYROSINE DEIODINASE bound to FMN and mono-iodotyrosine (MIT)
Structural highlights
Disease[IYD1_HUMAN] Familial thyroid dyshormonogenesis. The disease is caused by mutations affecting the gene represented in this entry. Function[IYD1_HUMAN] Catalyzes the oxidative NADPH-dependent deiodination of monoiodotyrosine (L-MIT) or diiodotyrosine (L-DIT). Acts during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways. Acts more efficiently on monoiodotyrosine than on diiodotyrosine.[1] Publication Abstract from PubMedReductive dehalogenation is not typical of aerobic organisms but plays a significant role in iodide homeostasis and thyroid activity. The flavoprotein iodotyrosine deiodinase (IYD) is responsible for iodide salvage by reductive deiodination of the iodotyrosine derivatives formed as byproducts of thyroid hormone biosynthesis. Heterologous expression of the human enzyme lacking its N-terminal membrane anchor has allowed for physical and biochemical studies to identify the role of substrate in controlling the active site geometry and flavin chemistry. Crystal structures of human IYD and its complex with 3-iodo-L-tyrosine illustrate the ability of the substrate to provide multiple interactions with the isoalloxazine system of FMN that are usually provided by protein side chains. Ligand binding acts to template the active site geometry and significantly stabilize the one electron reduced semiquinone form of FMN. The neutral form of this semiquinone is observed during reductive titration of IYD in the presence of the substrate analogue 3-fluoro-L-tyrosine. In the absence of an active site ligand, only the oxidized and two electron reduced forms of FMN are detected. The pH dependence of IYD binding and turnover also supports the importance of direct coordination between substrate and FMN for productive catalysis. A Switch Between One- and Two-Electron Chemistry of the Human Flavoprotein Iodotyrosine Deiodinase is Controlled by Substrate.,Hu J, Chuenchor W, Rokita SE J Biol Chem. 2014 Nov 13. pii: jbc.M114.605964. PMID:25395621[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||||||
