Database accession: MF7000523
Name: Mouse iodotyrosine deiodinase (IYD) C217A, C239A with FMN and mono-iodotyrosine (MIT)
PDB ID: 3tnz
Experimental method: X-ray (2.25 Å)
Assembly: Homodimer
Source organism: Mus musculus
Primary publication of the structure:
Buss JM, McTamney PM, Rokita SE
Expression of a soluble form of iodotyrosine deiodinase for active site characterization by engineering the native membrane protein from Mus musculus.
(2012) Protein Sci. 21: 351-61
PMID: 22238141
Abstract:
Reductive deiodination is critical for thyroid function and represents an unusual exception to the more common oxidative and hydrolytic mechanisms of dehalogenation in mammals. Studies on the reductive processes have been limited by a lack of convenient methods for heterologous expression of the appropriate proteins in large scale. The enzyme responsible for iodide salvage in the thyroid, iodotyrosine deodinase, is now readily generated after engineering its gene from Mus musculus. High expression of a truncated derivative lacking the membrane domain at its N-terminal was observed in Sf9 cells, whereas expression in Pichia pastoris remained low despite codon optimization. Ultimately, the desired expression in Escherichia coli was achieved after replacing the two conserved Cys residues of the deiodinase with Ala and fusing the resulting protein to thioredoxin. This final construct provided abundant enzyme for crystallography and mutagenesis. Utility of the E. coli system was demonstrated by examining a set of active site residues critical for binding to the zwitterionic portion of substrate.
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, B
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: 66-285)
Coverage: 77%
Name: Iodotyrosine deiodinase 1
Source organism: Mus musculus
Length: 285 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMFLLTPVLVAVVCILVVWVFKNADRNLEKKKEEAQVQPWVDEDLKDSTEDLQVEEDAEEWQEAEESVEHIPFSHTRYPEQEMRMRSQEFYELLNKRRSVRFISSEHVPMEVIENVIKAAGTAPSGAHTEPWTFVVVKDPDMKHKIREIIEEEEEINYMKRMGKRWVTDLKKLRTNWIKEYLDTAPVLILIFKQVHGFAANGKKKVHYYNEISVSIACGLLLAALQNAGLVTVTTTPLNCGPRLRVLLGRPSHEKLLVLLPVGYPSRDATVPDLKRKALDQIMVTV
UniProtKB AC: Q9DCX8 (positions: 66-285)
Coverage: 77%
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 B:
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)
Download this entry's JSON file (.json)
