Database accession: MF7000454
Name: Escherichia Coli Glyoxalase I (CD-bound)
PDB ID: 1fa7
Experimental method: X-ray (1.90 Å)
Assembly: Homodimer
Source organism: Escherichia coli
Primary publication of the structure:
He MM, Clugston SL, Honek JF, Matthews BW
Determination of the structure of Escherichia coli glyoxalase I suggests a structural basis for differential metal activation.
(2000) Biochemistry 39: 8719-27
PMID: 10913283
Abstract:
The metalloenzyme glyoxalase I (GlxI) converts the nonenzymatically produced hemimercaptal of cytotoxic methylglyoxal and glutathione to nontoxic S-D-lactoylglutathione. Human GlxI, for which the structure is known, is active in the presence of Zn(2+). Unexpectedly, the Escherichia coli enzyme is inactive in the presence of Zn(2+) and is maximally active with Ni(2+). To understand this difference in metal activation and also to obtain a representative of the bacterial enzymes, the structure of E. coli Ni(2+)-GlxI has been determined. Structures have also been determined for the apo enzyme as well as complexes with Co(2+), Cd(2+), and Zn(2+). It is found that each of the protein-metal complexes that is catalytically active has octahedral geometry. This includes the complexes of the E. coli enzyme with Ni(2+), Co(2+), and Cd(2+), as well as the structures reported for the human Zn(2+) enzyme. Conversely, the complex of the E. coli enzyme with Zn(2+) has trigonal bipyramidal coordination and is inactive. This mode of coordination includes four protein ligands plus a single water molecule. In contrast, the coordination in the active forms of the enzyme includes two water molecules bound to the metal ion, suggesting that this may be a key feature of the catalytic mechanism. A comparison of the human and E. coli enzymes suggests that there are differences between the active sites that might be exploited for therapeutic use.
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
nickel cation binding nickel cation binding
protein homodimerization activity protein homodimerization activity
Biological process:
methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione
response to toxic substance response to toxic substance
Cellular component:
cytoplasm cytoplasm
cytosol cytosol
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: Escherichia coli
Length: 135 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMRLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKYSLAFVGYGPETEEAVIELTYNWGVDKYELGTAYGHIALSVDNAAEACEKIRQNGGNVTREAGPVKGGTTVIAFVEDPDGYKIELIEEKDAGRGLGN
UniProtKB AC: P0AC81 (positions: 1-135)
Coverage: 100%
Name: Lactoylglutathione lyase
Source organism: Escherichia coli
Length: 135 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMRLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKYSLAFVGYGPETEEAVIELTYNWGVDKYELGTAYGHIALSVDNAAEACEKIRQNGGNVTREAGPVKGGTTVIAFVEDPDGYKIELIEEKDAGRGLGN
UniProtKB AC: P0AC81 (positions: 1-135)
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: 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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