Enzyme

1.1.1.169 - 2-dehydropantoate 2-reductase

Alternative Name(s)
  • Ketopantoic acid reductase.
  • KPA reductase.
  • Ketopantoate reductase.

Catalytic Activity

(R)-pantoate + NADP(+) = 2-dehydropantoate + H(+) + NADPH

Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

    Ketopantoate reductase (KPR), isolated from Escherichia coli, catalyses the reduction of ketopantoate by NADPH to form pantoate and NADP+. This is the second reaction in the pathway for the biosynthesis of pantothenate (vitamin B5). KPR is a member of the 6-phosphogluconate dehydrogenase superfamily. The reaction proceeds by a sequential ordered bi:bi kinetic mechanism, with NADPH binding first, followed by a conformational change and the binding of ketopantoate. After the reaction NADP+ dissociates first, followed by pantoate.

    The pro-S hydride of NADPH is transferred to the si face of the C2 carbonyl of ketopantoate. The developing alkoxide is protonated by Lys176 to form pantoate. Asn98 stabilises the active conformation of Lys176 and promotes the dissociation of NADP+.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Lys P0A9J4 176 1yon 176
    Step Components

    overall reactant used, overall product formed, proton transfer, bimolecular nucleophilic addition, aromatic unimolecular elimination by the conjugate base, native state of enzyme regenerated, inferred reaction step, cofactor used, hydride transfer

    Step 1.

    Initial binding of NADPH induces a conformational change that facilitates ketopantoate binding. Nucleophilic addition of the C4 pro-S hydride of NADPH to the si face of ketopantoate then occurs. The developing alkoxide is protonated by Lys176.

    Step 2.

    In an inferred reaction step Lys176 is reprotonated to regenerate the native state of the enzyme.

    Products.

    The products of the reaction.

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Protein name Organism
2-dehydropantoate 2-reductase Escherichia coli (strain K12)
Probable 2-dehydropantoate 2-reductase Fission yeast
Putative 2-dehydropantoate 2-reductase Mouse-ear cress
Plastidic glucose transporter 4 Stemphylium lycopersici
Putative dehydropantoate reductase Speckled leaf blotch fungus

Citations