Database accession: MF4120003
Name: 5-hydroxyisourate hydrolase (Bacillus subtilis)
PDB ID: 2h0e
Experimental method: X-ray (2.20 Å)
Assembly: Homotetramer
Source organism: Bacillus subtilis
Primary publication of the structure:
Jung DK, Lee Y, Park SG, Park BC, Kim GH, Rhee S
Structural and functional analysis of PucM, a hydrolase in the ureide pathway and a member of the transthyretin-related protein family.
(2006) Proc. Natl. Acad. Sci. U.S.A. 103: 9790-5
PMID: 16782815
Abstract:
The ureide pathway, which produces ureides from uric acid, is an essential purine catabolic process for storing and transporting the nitrogen fixed in leguminous plants and some bacteria. PucM from Bacillus subtilis was recently characterized and found to catalyze the second reaction of the pathway, hydrolyzing 5-hydroxyisourate (HIU), a product of uricase in the first step. PucM has 121 amino acid residues and shows high sequence similarity to the functionally unrelated protein transthyretin (TTR), a thyroid hormone-binding protein. Therefore, PucM belongs to the TTR-related proteins (TRP) family. The crystal structures of PucM at 2.0 A and its complexes with the substrate analogs 8-azaxanthine and 5,6-diaminouracil reveal that even with their overall structure similarity, homotetrameric PucM and TTR are completely different, both in their electrostatic potential and in the size of the active sites located at the dimeric interface. Nevertheless, the absolutely conserved residues across the TRP family, including His-14, Arg-49, His-105, and the C-terminal Tyr-118-Arg-119-Gly-120-Ser-121, indeed form the active site of PucM. Based on the results of site-directed mutagenesis of these residues, we propose a possible mechanism for HIU hydrolysis. The PucM structure determined for the TRP family leads to the conclusion that diverse members of the TRP family would function similarly to PucM as HIU hydrolase.
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
identical protein binding identical protein binding
Biological process:
purine nucleobase metabolic process purine nucleobase metabolic process
urate catabolic process urate catabolic process
Cellular component: not assigned
Structural annotations of the participating protein chains.Entry contents: 4 distinct polypeptide molecules
Chains: A-3, A, A-4, 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: Bacillus subtilis
Length: 114 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMGKLTTHILDLTCGKPAANVKIGLKRLGESIMKEVYTNNDGRVDVPLLAGEELMSGEYVMEFHAGDYFASKNMNAADQPFLTIVTVRFQLADPDAHYHIPLLLSPFGYQVYRGS
UniProtKB AC: O32142 (positions: 1-114)
Coverage: 100%
Name: 5-hydroxyisourate hydrolase
Source organism: Bacillus subtilis
Length: 114 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMGKLTTHILDLTCGKPAANVKIGLKRLGESIMKEVYTNNDGRVDVPLLAGEELMSGEYVMEFHAGDYFASKNMNAADQPFLTIVTVRFQLADPDAHYHIPLLLSPFGYQVYRGS
UniProtKB AC: O32142 (positions: 1-114)
Coverage: 100%
Name: 5-hydroxyisourate hydrolase
Source organism: Bacillus subtilis
Length: 114 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMGKLTTHILDLTCGKPAANVKIGLKRLGESIMKEVYTNNDGRVDVPLLAGEELMSGEYVMEFHAGDYFASKNMNAADQPFLTIVTVRFQLADPDAHYHIPLLLSPFGYQVYRGS
UniProtKB AC: O32142 (positions: 1-114)
Coverage: 100%
Name: 5-hydroxyisourate hydrolase
Source organism: Bacillus subtilis
Length: 114 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMGKLTTHILDLTCGKPAANVKIGLKRLGESIMKEVYTNNDGRVDVPLLAGEELMSGEYVMEFHAGDYFASKNMNAADQPFLTIVTVRFQLADPDAHYHIPLLLSPFGYQVYRGS
UniProtKB AC: O32142 (positions: 1-114)
Coverage: 100%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: -
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:16782815). 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 A-3:
N/A
Chain A-4:
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). No related structure was found in the MFIB database.
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