Database accession: MF7000527
Name: Iodotyrosine deiodinase (IYD) with FMN (Haliscomenobacter hydrossis)
PDB ID: 5ko7
Experimental method: X-ray (2.25 Å)
Assembly: Homodimer
Source organism: Haliscomenobacter hydrossis
Primary publication of the structure:
Ingavat N, Kavran JM, Sun Z, Rokita SE
Active Site Binding Is Not Sufficient for Reductive Deiodination by Iodotyrosine Deiodinase.
(2017) Biochemistry 56: 1130-1139
PMID: 28157283
Abstract:
The minimal requirements for substrate recognition and turnover by iodotyrosine deiodinase were examined to learn the basis for its catalytic specificity. This enzyme is crucial for iodide homeostasis and the generation of thyroid hormone in chordates. 2-Iodophenol binds only very weakly to the human enzyme and is dehalogenated with a kcat/Km that is more than 4 orders of magnitude lower than that for iodotyrosine. This discrimination likely protects against a futile cycle of iodinating and deiodinating precursors of thyroid hormone biosynthesis. Surprisingly, a very similar catalytic selectivity was expressed by a bacterial homologue from Haliscomenobacter hydrossis. In this example, discrimination was not based on affinity since 4-cyano-2-iodophenol bound to the bacterial deiodinase with a Kd lower than that of iodotyrosine and yet was not detectably deiodinated. Other phenols including 2-iodophenol were deiodinated but only very inefficiently. Crystal structures of the bacterial enzyme with and without bound iodotyrosine are nearly superimposable and quite similar to the corresponding structures of the human enzyme. Likewise, the bacterial enzyme is activated for single electron transfer after binding to the substrate analogue fluorotyrosine as previously observed with the human enzyme. A cocrystal structure of bacterial deiodinase and 2-iodophenol indicates that this ligand stacks on the active site flavin mononucleotide (FMN) in a orientation analogous to that of bound iodotyrosine. However, 2-iodophenol association is not sufficient to activate the FMN chemistry required for catalysis, and thus the bacterial enzyme appears to share a similar specificity for halotyrosines even though their physiological roles are likely very different from those in humans.
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
Biological process:
thyroid hormone metabolic process thyroid hormone metabolic process
tyrosine metabolic process tyrosine metabolic process
Cellular component: not assigned
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
Source organism: Haliscomenobacter hydrossis
Length: 222 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKQKPAFIPYAGAQFEPEEMLSKSAEYYQFMDHRRTVREFSNRAIPLEVIENIVMTASTAPSGAHKQPWTFVVVSDPQIKAKIRQAAEKEEFESYNGRMSNEWLEDLQPFGTDWHKPFLEIAPYLIVVFRKAYDVLPDGTQRKNYYVQESVGIACGFLLAAIHQAGLVALTHTPSPMNFLQKILQRPENERPFLLVPVGYPAEGAMVPDLQRKDKAAVMVVY
UniProtKB AC: F4KU78 (positions: 5-222)
Coverage: 98%
Name: Iodotyrosine deiodinase
Source organism: Haliscomenobacter hydrossis
Length: 222 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKQKPAFIPYAGAQFEPEEMLSKSAEYYQFMDHRRTVREFSNRAIPLEVIENIVMTASTAPSGAHKQPWTFVVVSDPQIKAKIRQAAEKEEFESYNGRMSNEWLEDLQPFGTDWHKPFLEIAPYLIVVFRKAYDVLPDGTQRKNYYVQESVGIACGFLLAAIHQAGLVALTHTPSPMNFLQKILQRPENERPFLLVPVGYPAEGAMVPDLQRKDKAAVMVVY
UniProtKB AC: F4KU78 (positions: 5-222)
Coverage: 98%
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)
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