Database accession: MF2100012
Name: Human glutathione S-transferase A1
PDB ID: 1k3y
Experimental method: X-ray (1.30 Å)
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
Le Trong I, Stenkamp RE, Ibarra C, Atkins WM, Adman ET
1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site.
(2002) Proteins 48: 618-27
PMID: 12211029
Abstract:
Cytosolic glutathione S-transferases (GSTs) play a critical role in xenobiotic binding and metabolism, as well as in modulation of oxidative stress. Here, the high-resolution X-ray crystal structures of homodimeric human GSTA1-1 in the apo form and in complex with S-hexyl glutathione (two data sets) are reported at 1.8, 1.5, and 1.3A respectively. At this level of resolution, distinct conformations of the alkyl chain of S-hexyl glutathione are observed, reflecting the nonspecific nature of the hydrophobic substrate binding site (H-site). Also, an extensive network of ordered water, including 75 discrete solvent molecules, traverses the open subunit-subunit interface and connects the glutathione binding sites in each subunit. In the highest-resolution structure, three glycerol moieties lie within this network and directly connect the amino termini of the glutathione molecules. A search for ligand binding sites with the docking program Molecular Operating Environment identified the ordered water network binding site, lined mainly with hydrophobic residues, suggesting an extended ligand binding surface for nonsubstrate ligands, the so-called ligandin site. Finally, detailed comparison of the structures reported here with previously published X-ray structures reveal a possible reaction coordinate for ligand-dependent conformational changes in the active site and the C-terminus.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
fatty acid binding fatty acid binding
glutathione peroxidase activity glutathione peroxidase activity
glutathione transferase activity glutathione transferase activity
steroid delta-isomerase activity steroid delta-isomerase activity
Biological process:
epithelial cell differentiation epithelial cell differentiation
glutathione derivative biosynthetic process glutathione derivative biosynthetic process
glutathione metabolic process glutathione metabolic process
linoleic acid metabolic process linoleic acid metabolic process
prostaglandin metabolic process prostaglandin metabolic process
xenobiotic metabolic process xenobiotic metabolic process
Cellular component:
cytosol cytosol
extracellular exosome extracellular exosome
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: Glutathione S-transferase A1
Source organism: Homo sapiens
Length: 222 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAEKPKLHYFNARGRMESTRWLLAAAGVEFEEKFIKSAEDLDKLRNDGYLMFQQVPMVEIDGMKLVQTRAILNYIASKYNLYGKDIKERALIDMYIEGIADLGEMILLLPVCPPEEKDAKLALIKEKIKNRYFPAFEKVLKSHGQDYLVGNKLSRADIHLVELLYYVEELDSSLISSFPLLKALKTRISNLPTVKKFLQPGSPRKPPMDEKSLEEARKIFRF
UniProtKB AC: P08263 (positions: 2-222)
Coverage: 99%
Name: Glutathione S-transferase A1
Source organism: Homo sapiens
Length: 222 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAEKPKLHYFNARGRMESTRWLLAAAGVEFEEKFIKSAEDLDKLRNDGYLMFQQVPMVEIDGMKLVQTRAILNYIASKYNLYGKDIKERALIDMYIEGIADLGEMILLLPVCPPEEKDAKLALIKEKIKNRYFPAFEKVLKSHGQDYLVGNKLSRADIHLVELLYYVEELDSSLISSFPLLKALKTRISNLPTVKKFLQPGSPRKPPMDEKSLEEARKIFRF
UniProtKB AC: P08263 (positions: 2-222)
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:
The urea-induced unfolding/refolding of human glutathione S-transferase A1 dimer has been shown to be a two-state process (PMID:9548764) with the association of disordered monomers forming a structured dimer. While there may be some structuring of the monomers before dimerization, this partial structure does not fully stabilize the protein (PMID:10600132).
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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