Investigating Phosphopantothenoylcysteine Synthetase as a Potential Antibacterial Target.

TL;DRAbstract

Phosphopantothenoylcysteine synthetase (PPCS) is the second enzyme in the universal Coenzyme A (CoA) biosynthetic pathway. PPCS is responsible for catalyzing the condensation of 4’-phosphopantothenate (PPA) and L-cysteine via nucleotide triphosphate activation of PPA. PPCSs have been broadly classified into three types (Type I-III) based upon expression profile and nucleotide triphosphate specificity. Type I PPCSs are found in a majority of bacteria and archaea, utilize CTP for activation of PPA in the first half reaction, and are expressed as the C-terminal domain of a fusion protein with phosphopantothenoylcysteine decarboxylase (PPCDC). Type II PPCSs are in eukaryotes, utilize both CTP and ATP, and expressed separately from PPCDC as a monofunctional enzyme. Type III PPCSs are found in certain bacteria, utilize CTP, and are expressed as a monofunctional enzyme. Based upon the difference in nucleotide triphosphate specificity and PPCS type between human and bacteria, PPCS was chosen f

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