Database accession: MF7000535
Name: Oxidized iodotyrosine deiodinase (IYD) with to FMN and L-Tyrosine
PDB ID: 6pz0
Experimental method: X-ray (1.80 Å)
Assembly: Homodimer
Source organism: Thermotoga neapolitana
Primary publication of the structure:
Sun Z, Xu B, Spisak S, Kavran JM, Rokita SE
The minimal structure for iodotyrosine deiodinase function is defined by an outlier protein from the thermophilic bacterium Thermotoga neapolitana.
(2021) J. Biol. Chem. 297: 101385
PMID: 34748729
Abstract:
The nitroreductase superfamily of enzymes encompasses many flavin mononucleotide (FMN)-dependent catalysts promoting a wide range of reactions. All share a common core consisting of an FMN-binding domain, and individual subgroups additionally contain one to three sequence extensions radiating from defined positions within this core to support their unique catalytic properties. To identify the minimum structure required for activity in the iodotyrosine deiodinase subgroup of this superfamily, attention was directed to a representative from the thermophilic organism Thermotoga neapolitana (TnIYD). This representative was selected based on its status as an outlier of the subgroup arising from its deficiency in certain standard motifs evident in all homologues from mesophiles. We found that TnIYD lacked a typical N-terminal sequence and one of its two characteristic sequence extensions, neither of which was found to be necessary for activity. We also show that TnIYD efficiently promotes dehalogenation of iodo-, bromo-, and chlorotyrosine, analogous to related deiodinases (IYDs) from humans and other mesophiles. In addition, 2-iodophenol is a weak substrate for TnIYD as it was for all other IYDs characterized to date. Consistent with enzymes from thermophilic organisms, we observed that TnIYD adopts a compact fold and low surface area compared with IYDs from mesophilic organisms. The insights gained from our investigations on TnIYD demonstrate the advantages of focusing on sequences that diverge from conventional standards to uncover the minimum essentials for activity. We conclude that TnIYD now represents a superior starting structure for future efforts to engineer a stable dehalogenase targeting halophenols of environmental concern.
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
L-tyrosine binding L-tyrosine binding
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: Thermotoga neapolitana
Length: 186 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKMLYDLAKKRKTVRRFKKEKPPLEDLIYSLKVANEAPSGMNAQPWRFLIVEDEKLKGQIRRVCERSEKTFYENVRGRLKEWLDEKRFTWRKPFLKEAPYLLLVFSEKSAPYSRESVWLAVGYLLLALEEKGLGSVPYTPPDFREVEKLVNTPSELRLEVILPVGYPDDPKPKYPRNEVIVRYNTF
UniProtKB AC: B9K712 (positions: 2-186)
Coverage: 99%
Name: Iodotyrosine deiodinase
Source organism: Thermotoga neapolitana
Length: 186 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKMLYDLAKKRKTVRRFKKEKPPLEDLIYSLKVANEAPSGMNAQPWRFLIVEDEKLKGQIRRVCERSEKTFYENVRGRLKEWLDEKRFTWRKPFLKEAPYLLLVFSEKSAPYSRESVWLAVGYLLLALEEKGLGSVPYTPPDFREVEKLVNTPSELRLEVILPVGYPDDPKPKYPRNEVIVRYNTF
UniProtKB AC: B9K712 (positions: 3-186)
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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