The iodothyronine selenodeiodinases are thioredoxin-fold family proteins containing a glycoside hydrolase clan GH-A-like structure.
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.
Callebaut
Isabelle
I
Poôle Bio, Laboratoive de Minéralogie-Cristallographie de Paris, CNRS UMR7590, Universities Paris 6 and Paris 7, Paris 75252 Cedex 05, France.
Curcio-Morelli
Cyntia
C
Mornon
Jean-P
JP
Gereben
Balazs
B
Buettner
Christoph
C
Huang
Stephen
S
Castro
Bertrand
B
Fonseca
Tatiana L
TL
Harney
John W
JW
Larsen
P Reed
PR
Bianco
Antonio C
AC
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
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