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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1mek

E.C. nameprotein disulfide-isomerase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 5.3.4.1
CSA Homologues of 1mekThere are 141 Homologs
CSA Entries With UniProtID P07237
CSA Entries With EC Number 5.3.4.1
PDBe Entry 1mek
PDBSum Entry 1mek
MACiE Entry M0191

Literature Report

IntroductionProtein disulfide isomerase (PDI) from humans is a 57 kDa protein present in the endoplasmic reticulum of eukaryotes. It is involved in disulfide bond formation, breakage, and rearrangement during the folding of proteins translocated into the endoplasmic reticulum. PDI contains two active sites with the amino acid sequence -Cys-Gly-His-Cys-, each of which is cycled between the dithiol and the disulfide forms as in the related redox protein thioredoxin. In addition, PDI is the beta subunit of prolyl-4-hydroxylase, which has an alpha2beta2 quaternary structure, and it is one subunit of the heterodimeric triglyceride transfer protein complex.
MechansimThe thiolate of Cys36 attacks the first of the disulfide bonds in a nucleophilic substitution reaction that results in an enzyme bound intermediate with a new thiolate. The newly formed thiolate attacks the second of the disulfide bonds in a nucleophilic substitution reaction that results in a new disulfide bond and second thiolate. The second newly formed thiolate attacks the disulfide bond between the intermediate and the Cys36 in a nucleophilic substitution reaction that results in the final new disulfide bond and free Cys36 thiolate.
With complex substrates (i.e. those with more than 2 disulfide bonds) this enzyme uses both catalytic cysteines (Cys36 and Cys39). With simple substrates (i.e. those with only 2 disulfide bonds) this enzyme uses only Cys36.

Catalytic Sites for 1mek

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
CysA3653macie:sideChainIn the deprotonated form acts as a nucleophile to a pre-existing disulphide bond.
CysA3956macie:sideChainIn the deprotonated form acts as a nucleophile to a pre-existing disulphide bond.
GlyA3754macie:sideChainPutatively acts to modulate pKa of neighbouring cysteine.
HisA3855macie:sideChainPutatively acts to modulate pKa of neighbouring cysteine.

Literature References

Notes:
Darby NJ
Characterization of the active site cysteine residues of the thioredoxin-like domains of protein disulfide isomerase.
Biochemistry 1995 34 16770-16780
PubMed: 8527452
Kemmink J
Structure determination of the N-terminal thioredoxin-like domain of protein disulfide isomerase using multidimensional heteronuclear 13C/15N NMR spectroscopy.
Biochemistry 1996 35 7684-7691
PubMed: 8672469
Kersteen EA
Catalysis of protein disulfide bond isomerization in a homogeneous substrate.
Biochemistry 2005 44 12168-12178
PubMed: 16142915
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