Enzyme - PreQ(1) synthase

Alternative Name(s)
  • PreQ(0) oxidoreductase.
  • PreQ(0) reductase.
  • 7-cyano-7-deazaguanine reductase.

Catalytic Activity

7-aminomethyl-7-carbaguanine + 2 NADP(+) = 7-cyano-7-deazaguanine + 3 H(+) + 2 NADPH


There are no Cofactors for this Enzyme

Reaction Mechanism

    First discovered from the biosynthetic pathway of queuosine, QueF nitrile reductase is part of the tRNA biosynthetic pathway in the cytosol of bacteria. The role of QueF in this pathway is to catalyse the NADPH-dependent reduction of 7-cyano-7-deazaguanine (preQ0) to 7-aminomethyl-7-deazaguanine (preQ1) by a unique four-electron reduction of nitrile to amine. This pathway is crucial for the pathogenicity of bacteria and has the potential to be used in industrial catalysis of organic compounds.

    The nitrile to amine conversion begins with the orientation of the substrate by seven key residues. The first stage of the mechanism is the activation of Cys194 by Asp201 which subsequently attacks the carbon of the nitrile group to form a C-S covalent bond. Secondly, NADPH facilitates a hydride transfer to the thoimidate intermediate. Then, following cleavage of the C-S bond a second hydride transfer occurs by a second NADPH molecule in the active site, forming the amine product.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Cys 188 3uxj 197
    Asp 195 3uxj 204
    His 227 3uxj 236
    Thr 191 3uxj 200
    Glu 228 3uxj 237
    Step Components

    overall product formed, proton transfer, unimolecular elimination by the conjugate base, bimolecular nucleophilic addition, intermediate formation, rate-determining step, inferred reaction step, intermediate collapse, hydride transfer

    Step 1.

    Asp201 activates Cys194 by deprotonation.

    Step 2.

    Cys194 performs a nucleophilic attack on the nitrile carbon, forming a thioimidate intermediate.

    Step 3.

    Protonation of Asp201 and the substrate; inferred by curator.

    Step 4.

    Hydride transfer from NADPH to substrate.

    Step 5.

    Cleavage of C-S covalent bond.

    Step 6.

    Cys194 protonation by Asp201.

    Step 7.

    Hydride transfer from a second NADPH molecule to carbon atom of imine.

    Step 8.

    Protonation of amine group by water molecule from bulk solvent. Inferred by curator; protonation may occur outside active site.


    The products of the reaction.

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Protein name Organism
NADPH-dependent 7-cyano-7-deazaguanine reductase Escherichia coli (strain K12)
Putative NADPH-dependent 7-cyano-7-deazaguanine reductase Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Queuine synthase Acinetobacter baumannii Naval-57
7-cyano-7-deazaguanine reductase ( queF) uncultured marine thaumarchaeote AD1000_100_C06
Outer membrane efflux protein Haemophilus influenzae