spacer
View the latest EBI news stories and important announcements...
more

spacer
Search The CSA
PDB ID
UNIPROT ID
EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1get

E.C. nameglutathione-disulfide reductase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 1.8.1.7
CSA Homologues of 1getThere are 103 Homologs
CSA Entries With UniProtID P06715
CSA Entries With EC Number 1.8.1.7
PDBe Entry 1get
PDBSum Entry 1get
MACiE Entry 1get

Literature Report

IntroductionThe pyrimidine nucleotide-disulphide oxidoreductases are a family of proteins which transfer electrons from NAD(P)H via FAD to a redox-active disulphide bond in the enzyme active site, which then reduces the substrate. The structure of the ubiquitous enzyme glutathione reductase (EC 1.6.4.2), which helps protect cells from oxidative stress, is similar to trypanothione reductase (EC 1.6.4.8), lipoamide dehydrogenase (EC 1.8.1.4), higher eukaryotic thioredoxin reductase (EC 1.6.4.5) and mercuric reductase (1.16.1.1).
MechansimInitially, the enzyme is in the oxidised state, with its redox active cysteines 42 and 47 (numbering for E. coli glutathione reductase) forming a disulphide bond to each other. Hydride is transferred from NAD(P)H to FAD, a process facilitated by Glu181, Lys50 and Tyr177, as demonstrated by mutagenesis and structural studies. From there the electron makes an SN2 attack on the sulphur atom of Cys47, causing Cys42 to be displaced as thiolate. This residue is now ready to attack the substrate, which in all cases except mercuric reductase is another disulphide bond. His439 from the other subunit of the dimer has an essential role here, as shown by mutagenesis; first it seems to withdraw a proton from Cys42, activating the latter residue for a nucleophilic attack on the substrate. The proton is then poised to polarise the resulting Cys42-substrate mixed disulphide bond, making it vulnerable to attack from Cys47 to return the enzyme to its rest state. In addition to His439, another residue from the second subunit is found in the active site: Glu444 is shown to be essential by mutagenesis, and in structures is seen to orientate the catalytic Histidine.
Reaction

Catalytic Sites for 1get

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
CysA4242macie:sideChain
CysA4747macie:sideChain
HisB439439macie:sideChain
GluB444444macie:sideChain

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA439439macie:sideChainError
GluA444444macie:sideChainError
GluB181181macie:sideChainError
CysB4242macie:sideChainError
CysB4747macie:sideChainError
TyrB177177macie:sideChainError
LysB5050macie:sideChainError

Literature References

Notes:
Pai EF
The catalytic mechanism of glutathione reductase as derived from x-ray diffraction analyses of reaction intermediates.
J Biol Chem 1983 258 1752-1757
PubMed: 6822532
Karplus PA
Substrate binding and catalysis by glutathione reductase as derived from refined enzyme: substrate crystal structures at 2 A resolution.
J Mol Biol 1989 210 163-180
PubMed: 2585516
spacer
spacer