title: The iodothyronine selenodeiodinases are thioredoxin-fold family proteins containing a glycoside hydrolase clan GH-A-like structure.
abstract: The three iodothyronine selenodeiodinases catalyze the initiation and termination of thyroid hormone effects in vertebrates. Structural analyses of these proteins have been hindered by their integral membrane nature and the inefficient eukaryotic-specific pathway for selenoprotein synthesis. Hydrophobic cluster analysis used in combination with Position-specific Iterated BLAST reveals that their extramembrane portion belongs to the thioredoxin-fold superfamily for which experimental structure information exists. Moreover, a large deiodinase region imbedded in the thioredoxin fold shares strong similarities with the active site of iduronidase, a member of the clan GH-A-fold of glycoside hydrolases. This model can explain a number of results from previous mutagenesis analyses and permits new verifiable insights into the structural and functional properties of these enzymes.
authors.affiliation: Poôle Bio, Laboratoive de Minéralogie-Cristallographie de Paris, CNRS UMR7590, Universities Paris 6 and Paris 7, Paris 75252 Cedex 05, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Callebaut
authors.forename: Cyntia
authors.initials: C
authors.lastname: Curcio-Morelli
authors.forename: Jean-P
authors.initials: JP
authors.lastname: Mornon
authors.forename: Balazs
authors.initials: B
authors.lastname: Gereben
authors.forename: Christoph
authors.initials: C
authors.lastname: Buettner
authors.forename: Stephen
authors.initials: S
authors.lastname: Huang
authors.forename: Bertrand
authors.initials: B
authors.lastname: Castro
authors.forename: Tatiana L
authors.initials: TL
authors.lastname: Fonseca
authors.forename: John W
authors.initials: JW
authors.lastname: Harney
authors.forename: P Reed
authors.initials: PR
authors.lastname: Larsen
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Bianco
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D002460:Cell Line; D019992:Databases as Topic; D004305:Dose-Response Relationship, Drug; D006026:Glycoside Hydrolases / Q000737:chemistry; D006801:Humans; D007453:Iodide Peroxidase / Q000737:chemistry* / Q000502:physiology*; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010940:Plant Proteins / Q000737:chemistry; D016133:Polymerase Chain Reaction; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013879:Thioredoxins / Q000737:chemistry; D013963:Thyroid Hormones / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D001426:Bacterial Proteins; D006026:Glycoside Hydrolases; D007453:Iodide Peroxidase; D010940:Plant Proteins; D013879:Thioredoxins; D013963:Thyroid Hormones; D000097564:Iodothyronine Deiodinase Type II; C109812:iodothyronine deiodinase type I; C117274:iodothyronine deiodinase type III