Enzyme - Phosphopantothenate--cysteine ligase (CTP)

Alternative Name(s)
  • Phosphopantothenoylcysteine synthetase.
  • Phosphopantothenate--cysteine ligase.

Catalytic Activity

(R)-4'-phosphopantothenate + CTP + L-cysteine = CMP + diphosphate + H(+) + N-[(R)-4-phosphopantothenoyl]-L-cysteine


There are no Cofactors for this Enzyme

Reaction Mechanism

    Phosphopantothenoylcysteine (PPC) synthase is a CTP-dependent enzyme joining L-cysteine to 4'-phosphopantothenate via a peptide bond. This reaction is part of the coenzyme A biosynthesis pathway. In E. coli, PPC synthase activity is performed by the CoaB domain of the bifunctional Dfp protein, with the next step of decarboxylation performed by the CoaC domain. Both domains have catalytic activity on their own.

    Much of the catalytic role of PPC synthase is due to the binding of substrates in the correct positions for reaction. The first half of the reaction attaches CMP onto phosphopantothenate. The carboxylate group of pantothenate is nucleophilic and attacks the alpha-phosphate of CTP (probably activated as an electrophile by coordination to a magnesium ion). Diphosphate is the leaving group, and the activated intermediate 4'-phosphopantothenoyl-CMP is formed. L-cysteine can now bind and its amino group attacks the carbonyl carbon of the ester group. This forms a tetrahedral transition state; the developing negative charge on the carbonyl oxygen is stabilised by a water molecule held by Asn 210. The transition state collapses to form CMP and the product.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Asn P0ABQ0 210 1u7u 30

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Protein name Organism
Phosphopantothenate--cysteine ligase CAB2 Baker's yeast
Phosphopantothenate--cysteine ligase 2 Mouse-ear cress
Phosphopantothenate--cysteine ligase 1 Mouse-ear cress
Coenzyme A biosynthesis bifunctional protein CoaBC Escherichia coli (strain K12)
Probable Phosphopantothenate--cysteine ligase Flavobacterium indicum (strain DSM 17447 / CIP 109464 / GPTSA100-9)