Database accession: MF7000521
Name: Mouse iodotyrosine deiodinase (IYD) with FMN
PDB ID: 3gb5
Experimental method: X-ray (2.00 Å)
Assembly: Homodimer
Source organism: Mus musculus
Primary publication of the structure:
Thomas SR, McTamney PM, Adler JM, Laronde-Leblanc N, Rokita SE
Crystal structure of iodotyrosine deiodinase, a novel flavoprotein responsible for iodide salvage in thyroid glands.
(2009) J. Biol. Chem. 284: 19659-67
PMID: 19436071
Abstract:
The flavoprotein iodotyrosine deiodinase (IYD) salvages iodide from mono- and diiodotyrosine formed during the biosynthesis of the thyroid hormone thyroxine. Expression of a soluble domain of this membrane-bound enzyme provided sufficient material for crystallization and characterization by x-ray diffraction. The structures of IYD and two co-crystals containing substrates, mono- and diiodotyrosine, alternatively, were solved at resolutions of 2.0, 2.45, and 2.6 A, respectively. The structure of IYD is homologous to others in the NADH oxidase/flavin reductase superfamily, but the position of the active site lid in IYD defines a new subfamily within this group that includes BluB, an enzyme associated with vitamin B(12) biosynthesis. IYD and BluB also share key interactions involving their bound flavin mononucleotide that suggest a unique catalytic behavior within the superfamily. Substrate coordination to IYD induces formation of an additional helix and coil that act as an active site lid to shield the resulting substrate.flavin complex from solvent. This complex is stabilized by aromatic stacking and extensive hydrogen bonding between the substrate and flavin. The carbon-iodine bond of the substrate is positioned directly over the C-4a/N-5 region of the flavin to promote electron transfer. These structures now also provide a molecular basis for understanding thyroid disease based on mutations of IYD.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
FMN binding FMN binding
iodotyrosine deiodinase activity iodotyrosine deiodinase activity
oxidoreductase activity oxidoreductase activity
Biological process:
thyroid hormone metabolic process thyroid hormone metabolic process
tyrosine metabolic process tyrosine metabolic process
Cellular component:
cytoplasmic vesicle membrane cytoplasmic vesicle membrane
nucleoplasm nucleoplasm
plasma membrane plasma membrane
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, A-2
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Iodotyrosine deiodinase 1
Source organism: Mus musculus
Length: 285 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMFLLTPVLVAVVCILVVWVFKNADRNLEKKKEEAQVQPWVDEDLKDSTEDLQVEEDAEEWQEAEESVEHIPFSHTRYPEQEMRMRSQEFYELLNKRRSVRFISSEHVPMEVIENVIKAAGTAPSGAHTEPWTFVVVKDPDMKHKIREIIEEEEEINYMKRMGKRWVTDLKKLRTNWIKEYLDTAPVLILIFKQVHGFAANGKKKVHYYNEISVSIACGLLLAALQNAGLVTVTTTPLNCGPRLRVLLGRPSHEKLLVLLPVGYPSRDATVPDLKRKALDQIMVTV
UniProtKB AC: Q9DCX8 (positions: 68-285)
Coverage: 76%
Name: Iodotyrosine deiodinase 1
Source organism: Mus musculus
Length: 285 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMFLLTPVLVAVVCILVVWVFKNADRNLEKKKEEAQVQPWVDEDLKDSTEDLQVEEDAEEWQEAEESVEHIPFSHTRYPEQEMRMRSQEFYELLNKRRSVRFISSEHVPMEVIENVIKAAGTAPSGAHTEPWTFVVVKDPDMKHKIREIIEEEEEINYMKRMGKRWVTDLKKLRTNWIKEYLDTAPVLILIFKQVHGFAANGKKKVHYYNEISVSIACGLLLAALQNAGLVTVTTTPLNCGPRLRVLLGRPSHEKLLVLLPVGYPSRDATVPDLKRKALDQIMVTV
UniProtKB AC: Q9DCX8 (positions: 68-285)
Coverage: 76%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Nitroreductase family
Evidence level: Indirect evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
Authors claim that the homodimeric NAD(P)H nitroreductase is a highly intertwined dimer with the FMN binding site lying at the dimer interface (PMID:18241886). Other structures belonging to the nitroreductase family also have an extensive interaction surface wherein a large hydrophobic solvent-accessible surface becomes buried upon dimer formation, suggesting that the monomers would be unstable on their own (PMID:16229462, PMID:19436071). Domain-swapping is also typical, where the extended C-terminal region extensively interacts with the core domain of the neighbouring monomer, forming an interlocked dimer (PMID:34473996, PMID:19436071, PMID:8885832).
Chain A:
N/A
Chain A-2:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
Download this entry's XML file (.xml)
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