Database accession: MF4120002
Name: 5-hydroxyisourate hydrolase (Salmonella dublin)
PDB ID: 2gpz
Experimental method: X-ray (2.50 Å)
Assembly: Homotetramer
Source organism: Salmonella dublin
Primary publication of the structure:
Hennebry SC, Law RH, Richardson SJ, Buckle AM, Whisstock JC
The crystal structure of the transthyretin-like protein from Salmonella dublin, a prokaryote 5-hydroxyisourate hydrolase.
(2006) J. Mol. Biol. 359: 1389-99
PMID: 16787778
Abstract:
The mechanism of binding of thyroid hormones by the transport protein transthyretin (TTR) in vertebrates is structurally well characterised. However, a homologous family of transthyretin-like proteins (TLPs) present in bacteria as well as eukaryotes do not bind thyroid hormones, instead they are postulated to perform a role in the purine degradation pathway and function as 5-hydroxyisourate hydrolases. Here we describe the 2.5 Angstroms X-ray crystal structure of the TLP from the Gram-negative bacterium Salmonella dublin, and compare and contrast its structure with vertebrate TTRs. The overall architecture of the homotetramer is conserved and, despite low sequence homology with vertebrate TTRs, structural differences within the monomer are restricted to flexible loop regions. However, sequence variation at the dimer-dimer interface has profound consequences for the ligand binding site and provides a structural rationalisation for the absence of thyroid hormone binding affinity in bacterial TLPs: the deep, negatively charged thyroxine-binding pocket that characterises vertebrate TTR contrasts with a shallow and elongated, positively charged cleft in S. dublin TLP. We have demonstrated that Sdu_TLP is a 5-hydroxyisourate hydrolase. Furthermore, using site-directed mutagenesis, we have identified three conserved residues located in this cleft that are critical to the enzyme activity. Together our data reveal that the active site of Sdu_TLP corresponds to the thyroxine binding site in TTRs.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
hydroxyisourate hydrolase activity hydroxyisourate hydrolase activity
Biological process:
purine nucleobase metabolic process purine nucleobase metabolic process
Cellular component:
periplasmic space periplasmic space
Structural annotations of the participating protein chains.Entry contents: 4 distinct polypeptide molecules
Chains: A, C, C-2, A-2
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: 5-hydroxyisourate hydrolase
Source organism: Salmonella dublin
Length: 136 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKRHILATVIASLVAAPAMALAAGNNILSVHILDQQTGKPAPGVEVVLEQKKDNGWTQLNTGHTDQDGRIKALWPEKAAAPGDYRVIFKTGQYFESKKLDTFFPEIPVEFHISKTNEHYHVPLLLSQYGYSTYRGS
UniProtKB AC: Q4VYA5 (positions: 27-136)
Coverage: 80%
Name: 5-hydroxyisourate hydrolase
Source organism: Salmonella dublin
Length: 136 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKRHILATVIASLVAAPAMALAAGNNILSVHILDQQTGKPAPGVEVVLEQKKDNGWTQLNTGHTDQDGRIKALWPEKAAAPGDYRVIFKTGQYFESKKLDTFFPEIPVEFHISKTNEHYHVPLLLSQYGYSTYRGS
UniProtKB AC: Q4VYA5 (positions: 27-136)
Coverage: 80%
Name: 5-hydroxyisourate hydrolase
Source organism: Salmonella dublin
Length: 136 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKRHILATVIASLVAAPAMALAAGNNILSVHILDQQTGKPAPGVEVVLEQKKDNGWTQLNTGHTDQDGRIKALWPEKAAAPGDYRVIFKTGQYFESKKLDTFFPEIPVEFHISKTNEHYHVPLLLSQYGYSTYRGS
UniProtKB AC: Q4VYA5 (positions: 27-136)
Coverage: 80%
Name: 5-hydroxyisourate hydrolase
Source organism: Salmonella dublin
Length: 136 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKRHILATVIASLVAAPAMALAAGNNILSVHILDQQTGKPAPGVEVVLEQKKDNGWTQLNTGHTDQDGRIKALWPEKAAAPGDYRVIFKTGQYFESKKLDTFFPEIPVEFHISKTNEHYHVPLLLSQYGYSTYRGS
UniProtKB AC: Q4VYA5 (positions: 27-136)
Coverage: 80%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: HIUase/Transthyretin family
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The protein belongs to the 5-hydroxyisourate hydrolase (HIUase)/transthyretin protein family. Accordingly, the complex adopts a transthyterin-like fold (based on Pfam entry PF00576.18 and the publication PMID:16787778). Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID:11152276).
Chain A:
N/A
Chain C:
N/A
Chain C-2:
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)
Download this entry's JSON file (.json)
