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Catalytic Site Atlas

CSA LITERATURE entry for 1qfn

E.C. nameribonucleoside-diphosphate reductase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 1.17.4.1
CSA Homologues of 1qfnThere are 13 Homologs
CSA Entries With UniProtID P00452
CSA Entries With EC Number 1.17.4.1
PDBe Entry 1qfn
PDBSum Entry 1qfn
MACiE Entry 1qfn

Literature Report

Introduction Deoxyribonucleotide synthesis requires the reduction of the the C2' atom of ribonucleotides. Ribonucleotide reductase (RNR) catalyses this reaction via the formation of a disulfide bond in RNR itself. To regenerate active RNR, this disulfide must be reduced; glutaredoxin (Grx) is one of the enzymes which does this.
MechansimOxidoreduction is via the formation and breaking of disulfide bonds between cysteine side groups:
Oxidised RNR has a disulfide bond between Cys 143 and Cys 148. Cys 11 of Grx is nucleophilic and attacks Cys 148 in an SN2 fashion to break the Cys 143-Cys 148 bond. Cys 14 is in a low pKa environment and is nucleophilic; it attacks Cys 11 in an SN2 fashion to break the Cys 148-Cys 11 bond. Thus, the disulfide bond of RNR is transferred to Grx.
Reaction

Catalytic Sites for 1qfn

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrA1313macie:sideChainTyr13 stabilises the transition state for the formation of the Cys754 thiol and helps to prevent the reaction from reversing.
ArgA88macie:sideChainArg8 decreases the pKa of Cys11, making it more nucleophilic. It also increases the negative electrostatic potential surrounding Cys14, making it more nucleophilic.
GlyA1010macie:mainChainAmideGly10 is thought to be involved in proton transfer from Cys14 to the solvent.
LysA1818macie:sideChainLys18 increases the negative electrostatic potential surrounding Cys14, making it more nucleophilic.
TyrA7272macie:sideChainTyr72 stabilises the transition state for the formation of the Cys754 thiol and helps to prevent the reaction from reversing.

Literature References

Notes: The numbering of Cys 143 and Cys 148 for the substrate molecule RNR B1 subunit refers to their numbering in this PDB entry. In the native RNR B1 they are Cys 754 and Cys 759 respectively. The residues effecting the low pKa of Cys 14 is not certain but is likely to involve positively charged residues around the active site. Similarly the mechanism of proton transfer in the buried active site is unclear, but may involve backbone amides to shuttle protons to and from the solvent.
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