Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

NADPH-dependent 7-cyano-7-deazaguanine reductase By Reference

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.




• Summary
• Step 1
• Step 2
• Step 3
• Step 4
• Step 5
• Step 6
• Step 7
• Step 8
• Products

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.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Citations

• Riboswitches, from cognition to transformation.
• Biosynthesis of three N-acetylaminosugar-conjugated flavonoids using engineered Escherichia coli.
• The Escherichia coli COG1738 Member YhhQ Is Involved in 7-Cyanodeazaguanine (preQ₀) Transport.
• Pantoea Bacteriophage vB_PagS_Vid5: A Low-Temperature Siphovirus That Harbors a Cluster of Genes Involved in the Biosynthesis of Archaeosine.
• Crystal structure of the archaeosine synthase QueF-like-Insights into amidino transfer and tRNA recognition by the tunnel fold.
• Identification of the minimal bacterial 2'-deoxy-7-amido-7-deazaguanine synthesis machinery.
• Regulation of Gene Expression Through Effector-dependent Conformational Switching by Cobalamin Riboswitches.
• Deazaguanine derivatives, examples of crosstalk between RNA and DNA modification pathways.
• A Riboswitch-Driven Era of New Antibacterials.
• Structure and function of preQ₁ riboswitches.
• The primary transcriptome of Neisseria meningitidis and its interaction with the RNA chaperone Hfq.