Database accession: MF7000496
Name: Human Glyoxalase I (with C-ter His tag)
PDB ID: 7wsz
Experimental method: X-ray (1.52 Å)
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
Usami M, Ando K, Shibuya A, Takasawa R, Yokoyama H
Crystal structures of human glyoxalase I and its complex with TLSC702 reveal inhibitor binding mode and substrate preference.
(2022) FEBS Lett. 596: 1458-1467
PMID: 35363883
Abstract:
Human glyoxalase I (hGLO I) is an enzyme for detoxification of methylglyoxal (MG) and has been considered an attractive target for the development of new anticancer drugs. In our previous report, the GLO I inhibitor TLSC702 induced apoptosis in tumor cells. Here, we determined the crystal structures of hGLO I and its complex with TLSC702. In the complex, the carboxyl O atom of TLSC702 is coordinated to Zn2+ , and TLSC702 mainly shows van der Waals interaction with hydrophobic residues. In the inhibitor-unbound structure, glycerol, which has similar functional groups to MG, was bound to Zn2+ , indicating that GLO I can easily bind to MG. This study provides a structural basis to develop better anticancer drugs.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
lactoylglutathione lyase activity lactoylglutathione lyase activity
zinc ion binding zinc ion binding
Biological process:
carbohydrate metabolic process carbohydrate metabolic process
glutathione metabolic process glutathione metabolic process
methylglyoxal metabolic process methylglyoxal metabolic process
negative regulation of apoptotic process negative regulation of apoptotic process
osteoclast differentiation osteoclast differentiation
regulation of transcription by RNA polymerase II regulation of transcription by RNA polymerase II
Cellular component:
cytoplasm cytoplasm
cytosol cytosol
extracellular exosome extracellular exosome
nucleoplasm nucleoplasm
plasma membrane plasma membrane
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: Lactoylglutathione lyase
Source organism: Homo sapiens
Length: 184 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAEPQPPSGGLTDEAALSCCSDADPSTKDFLLQQTMLRVKDPKKSLDFYTRVLGMTLIQKCDFPIMKFSLYFLAYEDKNDIPKEKDEKIAWALSRKATLELTHNWGTEDDETQSYHNGNSDPRGFGHIGIAVPDVYSACKRFEELGVKFVKKPDDGKMKGLAFIQDPDGYWIEILNPNKMATLM
UniProtKB AC: Q04760 (positions: 9-184)
Coverage: 95%
Name: Lactoylglutathione lyase
Source organism: Homo sapiens
Length: 184 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAEPQPPSGGLTDEAALSCCSDADPSTKDFLLQQTMLRVKDPKKSLDFYTRVLGMTLIQKCDFPIMKFSLYFLAYEDKNDIPKEKDEKIAWALSRKATLELTHNWGTEDDETQSYHNGNSDPRGFGHIGIAVPDVYSACKRFEELGVKFVKKPDDGKMKGLAFIQDPDGYWIEILNPNKMATLM
UniProtKB AC: Q04760 (positions: 9-182)
Coverage: 94%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily
Evidence level: Indirect evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The VOC superfamily of metalloenzymes is characterized by a three-dimensional domain-swapped arrangement of tandem βαβββ-motifs (PMID:24447055). The original gene duplication event led to the βαβββ tandem structure, which appears to require dimerization for stability. Two different forms of domain-swapped dimers may coexist in solution (PMID:12121648) in which both subunits of the homodimer participate in coordination of each metal ion and formation of the U-shaped active sites in the enzyme (PMID:24004181). The complex is predominantly dimeric in solution (gel filtration) (PMID:12121648).
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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