Database accession: MF2110018
Name: Glutathione S-transferase (Schistosoma japonicum)
PDB ID: 4wr4
Experimental method: X-ray (1.60 Å)
Assembly: Homodimer
Source organism: Schistosoma japonicum
Primary publication of the structure:
Ohtake K, Yamaguchi A, Mukai T, Kashimura H, Hirano N, Haruki M, Kohashi S, Yamagishi K, Murayama K, Tomabechi Y, Itagaki T, Akasaka R, Kawazoe M, Takemoto C, Shirouzu M, Yokoyama S, Sakamoto K
Protein stabilization utilizing a redefined codon.
(2015) Sci Rep 5: 9762
PMID: 25985257
Abstract:
Recent advances have fundamentally changed the ways in which synthetic amino acids are incorporated into proteins, enabling their efficient and multiple-site incorporation, in addition to the 20 canonical amino acids. This development provides opportunities for fresh approaches toward addressing fundamental problems in bioengineering. In the present study, we showed that the structural stability of proteins can be enhanced by integrating bulky halogenated amino acids at multiple selected sites. Glutathione S-transferase was thus stabilized significantly (by 5.2 and 5.6 kcal/mol) with 3-chloro- and 3-bromo-l-tyrosines, respectively, incorporated at seven selected sites. X-ray crystallographic analyses revealed that the bulky halogen moieties filled internal spaces within the molecules, and formed non-canonical stabilizing interactions with the neighboring residues. This new mechanism for protein stabilization is quite simple and applicable to a wide range of proteins, as demonstrated by the rapid stabilization of the industrially relevant azoreductase.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
glutathione transferase activity glutathione transferase activity
Biological process:
glutathione metabolic process glutathione metabolic process
Cellular component: not assigned
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, A-2
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Glutathione S-transferase class-mu 26 kDa isozyme
Source organism: Schistosoma japonicum
Length: 218 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSPILGYWKIKGLVQPTRLLLEYLEEKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSMAIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDFETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDALDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPLQGWQATFGGGDHPPK
UniProtKB AC: P08515 (positions: 2-217)
Coverage: 99%
Name: Glutathione S-transferase class-mu 26 kDa isozyme
Source organism: Schistosoma japonicum
Length: 218 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSPILGYWKIKGLVQPTRLLLEYLEEKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSMAIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDFETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDALDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPLQGWQATFGGGDHPPK
UniProtKB AC: P08515 (positions: 2-217)
Coverage: 99%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Glutathione S-transferase
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
Data of the urea- and temperature-induced unfolding of the dimer indicate the absence of thermodynamically stable intermediates and that the unfolding/refolding transition is a two-state process involving folded native dimer and unfolded monomer. Thermograms obtained by differential scanning microcalorimetry also fitted a two-state unfolding transition model (PMID:9041642).
Chain A:
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)
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